Ignet

Gene Information

Gene symbol: TLR1

Gene name: toll-like receptor 1

HGNC ID: 11847

Synonyms: rsc786, KIAA0012, CD281

Related Genes

#	Gene Symbol	Number of hits
1	APC	1 hits
2	BCR	1 hits
3	CD14	1 hits
4	CD3G	1 hits
5	CD4	1 hits
6	CD40	1 hits
7	CD8A	1 hits
8	CELIAC3	1 hits
9	CSK	1 hits
10	CTLA4	1 hits
11	CXCL11	1 hits
12	CXCL9	1 hits
13	DDX58	1 hits
14	ENG	1 hits
15	FASLG	1 hits
16	HAVCR2	1 hits
17	HSPA1A	1 hits
18	IFIH1	1 hits
19	IFNG	1 hits
20	IL10	1 hits
21	IL1B	1 hits
22	IL2	1 hits
23	IL2RA	1 hits
24	IL4	1 hits
25	IL6	1 hits
26	IL7	1 hits
27	IL8	1 hits
28	LAG3	1 hits
29	LAMP3	1 hits
30	LGALS3	1 hits
31	MAPK1	1 hits
32	MAPK10	1 hits
33	MLANA	1 hits
34	MYCBP2	1 hits
35	NFKB1	1 hits
36	PDCD1	1 hits
37	PECAM1	1 hits
38	SCARA3	1 hits
39	SLA	1 hits
40	TBX21	1 hits
41	TERT	1 hits
42	TH1L	1 hits
43	TICAM2	1 hits
44	TLR2	1 hits
45	TLR3	1 hits
46	TLR4	1 hits
47	TLR5	1 hits
48	TLR6	1 hits
49	TLR7	1 hits
50	TLR9	1 hits
51	TNF	1 hits
52	VTCN1	1 hits

Related Sentences

#	PMID	Sentence
1	8402652	Also, TIL recovered from the responding lung metastasis and cultured in the presence of IL2 gave rise to autologous tumor-reactive CD4+ T-cells, whereas the nonresponsive renal tumor yielded a mixture of T- and natural killer cells.
2	9139889	The capacity of rVV-M to generate HLA-A2.1-restricted MART-1/Melan A-specific CTL was demonstrated from tumor-infiltrating-lymphocyte (TIL) cultures and from healthy donors' peripheral-blood mononuclear cells (PBMC).
3	9139889	MART-1/Melan-A27-35-specific CTL were generated from TIL after 2 weekly stimulation courses.
4	9139889	In addition, TNF-alpha production could be induced in rVV-M-stimulated CTL upon co-culture with COS-7 cells transiently transfected with MART-1/Melan-A and HLA-A2.1 genes.
5	9139889	The capacity of rVV-M to generate HLA-A2.1-restricted MART-1/Melan A-specific CTL was demonstrated from tumor-infiltrating-lymphocyte (TIL) cultures and from healthy donors' peripheral-blood mononuclear cells (PBMC).
6	9139889	MART-1/Melan-A27-35-specific CTL were generated from TIL after 2 weekly stimulation courses.
7	9139889	In addition, TNF-alpha production could be induced in rVV-M-stimulated CTL upon co-culture with COS-7 cells transiently transfected with MART-1/Melan-A and HLA-A2.1 genes.
8	9610908	When compared with exogenous IL-2, RCC-Ad-IL-2 induced less growth expansion of TILs whereas a reduced CD56+ (23 +/- 14% vs. 44 +/- 13%; p < 0.05) but increased CD3+CD4+ cell population (32 +/- 11% vs. 15 +/- 6%; p < 0.05) with enhanced T cell-receptor use (59 +/- 10% vs. 42 +/- 7%; p < 0.005) was determined.
9	9610908	An augmented human leukocyte antigen (HLA)-restricted and tumor-specific cytotoxicity was detected in RCC-Ad-IL-2-expanded TILs (day 35, 15.3 +/- 4.2 LU vs. 4.6 +/- 1.8 LU; p < 0.005).
10	9610908	These properties were mediated by the CD8+ and CD4+ T-cell populations, as demonstrated by antibody-blocking assays.
11	9610908	A unique cytokine profile also was detected in RCC-Ad-IL-2-induced TILs, which demonstrated an upregulation of both GM-CSF and IL-6 mRNA as compared with TILs expanded in the presence of exogenous IL-2.
12	11394496	MHC class II-restricted tumor antigens recognized by CD4+ T cells: new strategies for cancer vaccine design.
13	11394496	This finding has led to the identification and characterization of tumor-associated antigens recognized by CD8+ TIL.
14	11394496	These data suggest that it may be necessary to engage both CD4+ and CD8+ T cells for more effective antitumor immunotherapy.
15	11394496	In this report, we review emerging molecular approaches in cloning major histocompatibility complex (MHC) class II restricted tumor antigens recognized by CD4+ T cells as well as approaches to identify new MHC class II-restricted epitopes from known tumor antigens recognized by CD8+ cytotoxic T lymphocytes and/or antibodies.
16	11394496	More importantly, the discovery of MHC class II-restricted tumor antigens has provided opportunities for developing a new generation of cancer vaccines aimed at eliciting both CD4+ and CD8+ T-cell responses against tumor.
17	11395634	MHC Class II-Restricted Tumor Antigens Recognized by CD4+ T Cells: New Strategies for Cancer Vaccine Design.
18	11395634	This finding has led to the identification and characterization of tumor-associated antigens recognized by CD8+ TIL.
19	11395634	These data suggest that it may be necessary to engage both CD4+ and CD8+ T cells for more effective antitumor immunotherapy.
20	11395634	In this report, we review emerging molecular approaches in cloning major histocompatibility complex (MHC) class II restricted tumor antigens recognized by CD4+ T cells as well as approaches to identify new MHC class II-restricted epitopes from known tumor antigens recognized by CD8+ cytotoxic T lymphocytes and/or antibodies.
21	11395634	More importantly, the discovery of MHC class II-restricted tumor antigens has provided opportunities for developing a new generation of cancer vaccines aimed at eliciting both CD4+ and CD8+ T-cell responses against tumor.
22	11527700	T Lymphocytes infiltrating various tumour types express the MHC class II ligand lymphocyte activation gene-3 (LAG-3): role of LAG-3/MHC class II interactions in cell-cell contacts.
23	11527700	The product of the Lymphocyte Activation Gene-3 (LAG-3, CD223) is a high affinity MHC class II ligand expressed by activated CD4(+) and CD8(+) T cells, which can associate with the T cell receptor (TCR) and downregulate TCR signalling in vitro.
24	11527700	We have also reported that a soluble mLAG-3Ig fusion protein works as a vaccine adjuvant in vivo in mice, enhancing Th1 and CD8 T cell responses.
25	11527700	Here, we report that LAG-3 expression was found, using fluorescent activated cell sorting (FACS) analysis, on 11-48% of human tumour-infiltrating lymphocytes (TILs) isolated from eight freshly dissociated renal cell carcinomas (RCCs), and was restricted mostly to CD8(+) cells.
26	11527700	Since not only antigen presenting cells (APCs), but also TILs themselves strongly express major histocompatibility complex (MHC) class II, we firstly investigated whether LAG-3/MHC class II T-T cell contacts might influence tumour cell recognition.
27	11527700	In contrast, MHC class II engagement by LAG-3Ig was found to enhance the capacity of immature dendritic cells to stimulate naive T cell proliferation and IL-12-dependent IFN-gamma production by T cells in vitro.
28	11527700	These results therefore provide support for a role for TIL-expressed LAG-3 in the engagement of class II molecules on APCs, thereby contributing to APC activation and Th1/Tc1 commitment, without downregulating cytotoxicity.
29	12091878	Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice.
30	12091878	The macrophages of low responders produced less tumor necrosis factor-alpha and interleukin-6 after OspA stimulation and had lower cell-surface expression of Toll-like receptor (TLR) 1 as compared to normal cells, but normal expression of TLR2.
31	12091878	After OspA immunization, mice genetically deficient in either TLR2 (TLR2(-/-)) or TLR1 (TLR1(-/-)) produced low titers of antibodies against OspA.
32	12091878	Notably, macrophages from TLR2(-/-) mice were unresponsive to OspA and PGN, whereas those from TLR1(-/-) mice responded normally to PGN but not to OspA.
33	12091878	These data indicate that TLR1 and TLR2 are required for lipoprotein recognition and that defects in the TLR1/2 signaling pathway may account for human hyporesponsiveness to OspA vaccination.
34	12091878	Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice.
35	12091878	The macrophages of low responders produced less tumor necrosis factor-alpha and interleukin-6 after OspA stimulation and had lower cell-surface expression of Toll-like receptor (TLR) 1 as compared to normal cells, but normal expression of TLR2.
36	12091878	After OspA immunization, mice genetically deficient in either TLR2 (TLR2(-/-)) or TLR1 (TLR1(-/-)) produced low titers of antibodies against OspA.
37	12091878	Notably, macrophages from TLR2(-/-) mice were unresponsive to OspA and PGN, whereas those from TLR1(-/-) mice responded normally to PGN but not to OspA.
38	12091878	These data indicate that TLR1 and TLR2 are required for lipoprotein recognition and that defects in the TLR1/2 signaling pathway may account for human hyporesponsiveness to OspA vaccination.
39	12091878	Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice.
40	12091878	The macrophages of low responders produced less tumor necrosis factor-alpha and interleukin-6 after OspA stimulation and had lower cell-surface expression of Toll-like receptor (TLR) 1 as compared to normal cells, but normal expression of TLR2.
41	12091878	After OspA immunization, mice genetically deficient in either TLR2 (TLR2(-/-)) or TLR1 (TLR1(-/-)) produced low titers of antibodies against OspA.
42	12091878	Notably, macrophages from TLR2(-/-) mice were unresponsive to OspA and PGN, whereas those from TLR1(-/-) mice responded normally to PGN but not to OspA.
43	12091878	These data indicate that TLR1 and TLR2 are required for lipoprotein recognition and that defects in the TLR1/2 signaling pathway may account for human hyporesponsiveness to OspA vaccination.
44	12091878	Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice.
45	12091878	The macrophages of low responders produced less tumor necrosis factor-alpha and interleukin-6 after OspA stimulation and had lower cell-surface expression of Toll-like receptor (TLR) 1 as compared to normal cells, but normal expression of TLR2.
46	12091878	After OspA immunization, mice genetically deficient in either TLR2 (TLR2(-/-)) or TLR1 (TLR1(-/-)) produced low titers of antibodies against OspA.
47	12091878	Notably, macrophages from TLR2(-/-) mice were unresponsive to OspA and PGN, whereas those from TLR1(-/-) mice responded normally to PGN but not to OspA.
48	12091878	These data indicate that TLR1 and TLR2 are required for lipoprotein recognition and that defects in the TLR1/2 signaling pathway may account for human hyporesponsiveness to OspA vaccination.
49	12384805	In the group with only one invaded lymph node, the estimated relapse rate was significantly lower ( P(adjusted)=0.0285) and the overall survival was increased ( P(adjusted)=0.039) in the TIL+IL-2 arm compared with the IL-2 only arm.
50	12514169	Muramyl dipeptide was recognized by NOD2 but not by TLR2 or co-expression of TLR2 with TLR1 or TLR6.
51	12763684	Cells expressing Toll-like receptor (TLR), TLR2 in association with TLR1, TLR6 or some other unknown co-receptor can respond upon interaction with a large variety of microbial ligands.
52	12798304	Dual expression of CD80 and CD86 produces a tumor vaccine superior to single expression of either molecule.
53	12798304	An aggressive subclone of N2a and the less aggressive parental line were transfected with CD80, CD86, or both molecules and stable lines were established.
54	12798304	The less aggressive N2a expressing either CD80 or CD86 induced anti-tumor immunity.
55	12798304	In contrast, dual expression of CD80 and CD86 was required to initiate a protective anti-tumor immune response against the aggressive subclone.
56	12798304	Control of tumor growth was dependent on CD8+ lymphocytes that infiltrated dual-expressing (CD80 and CD86) lesions.
57	12798304	These tumor-infiltrating lymphocytes (TIL) exhibited a non-classical mechanism of tumor cell lysis that may require both the up-regulation of cell surface molecules on the tumor and the subsequent lytic activity normally associated with CD8+ TIL.
58	12798304	Although Fas was up-regulated by the tumor in the presence of IFN-gamma, N2a and transfected N2a cell lines were not sensitive to Fas-mediated lysis.
59	12804162	TLR2 may form heterodimers with TLR6 to identify diacylated lipoproteins, while TLR2 works in concert with TLR1 to recognize triacylated lipoproteins such as OspA.
60	12804162	We will discuss the role of TLR1/2 in the development of responses to OspA in TLR1-and TLR2-deficient mice, and in selected individuals that received the OspA vaccine.
61	12804162	Moreover, TLR1- and TLR2-deficient mice did not develop significant levels of OspA antibodies following vaccination with OspA, providing a correlation with human hyporesponsiveness to OspA.
62	12804162	TLR2 may form heterodimers with TLR6 to identify diacylated lipoproteins, while TLR2 works in concert with TLR1 to recognize triacylated lipoproteins such as OspA.
63	12804162	We will discuss the role of TLR1/2 in the development of responses to OspA in TLR1-and TLR2-deficient mice, and in selected individuals that received the OspA vaccine.
64	12804162	Moreover, TLR1- and TLR2-deficient mice did not develop significant levels of OspA antibodies following vaccination with OspA, providing a correlation with human hyporesponsiveness to OspA.
65	12804162	TLR2 may form heterodimers with TLR6 to identify diacylated lipoproteins, while TLR2 works in concert with TLR1 to recognize triacylated lipoproteins such as OspA.
66	12804162	We will discuss the role of TLR1/2 in the development of responses to OspA in TLR1-and TLR2-deficient mice, and in selected individuals that received the OspA vaccine.
67	12804162	Moreover, TLR1- and TLR2-deficient mice did not develop significant levels of OspA antibodies following vaccination with OspA, providing a correlation with human hyporesponsiveness to OspA.
68	15251043	Flow cytometry was performed to analyze cell phenotype in TILs and IFN-gamma ELISA was performed to detect antigen-specific immune response.
69	15251043	Interestingly, the CD8+ T cell population was increased in TILs of alpha-GalCer-treated mice, and the activation level of these cells based on CD69 expression was higher than that in vehicle-treated mice.
70	16425224	In this study, the treatment with heat shock protein 70 (HSP70) vaccine induced an infiltration of T cells into the tumor site as well as the expression of IFN-gamma and IL-2, and delayed lung metastases of tumor, but the tumor progression nonetheless occur finally.
71	16425224	To complement these findings, we investigated the gene expression of tumor-infiltrating lymphocytes (TILs) by Real-time PCR analysis, which revealed that the expression of TH1 cytokines IFN-gamma and IL-2 by TIL in the mice treated with HSP70 vaccine in combination with sPD-1 was increased and the expression of negative regulatory molecules IL-10, TGF-beta and foxp3 was decreased, demonstrating that multifunctional properties afforded by the combination therapy can effectively overcome tumor resistance and promote effective antitumor immunity.
72	16509590	Lipolanthionine peptides act as inhibitors of TLR2-mediated IL-8 secretion.
73	16509590	Lipoproteins from gram-positive and -negative bacteria, mycoplasma, and shorter synthetic lipopeptide analogues activate cells of the innate immune system via the Toll-like receptor TLR2/TLR1 or TLR2/TLR6 heterodimers.
74	16509590	A collection of analytically defined lipolanthionine peptide amides exhibited an inhibitory effect of the TLR2-mediated IL-8 secretion when applied in high molar excess to the agonistic synthetic lipopeptide Pam3Cys-Ser-(Lys)4-OH.
75	16574669	Induction of kappaB-driven transcriptional activity by 2.5 mug ml(-1) F. tularensis LPS isolated by phenol-water and ether-water extraction, was observed in cells transfected with Toll-like receptor (TLR) 4 and MD-2, although CD14 was required for optimal induction.
76	16574669	Conversely, TLR2, TLR2/TLR1 or TLR2/TLR6 transfected cells did not show kappaB-driven transcriptional activity in the presence of F. tularensis LPS.
77	16574669	Concentrations of 5-10 mug ml(-1) F. tularensis LPS elicited a similar pattern of mRNA and protein induction than 0.1 mug ml(-1) E. coli LPS, including the expression of CXC chemokines (IL-8, Gro and IFN-gamma-inducible protein-10); CC chemokines (monocyte chemoattractant protein-1 and -2, macrophage-derived chemoattractant, macrophage inflammatory protein-1alpha and -1beta and RANTES (regulated upon activation, normal T cell expressed and secreted) and pro-inflammatory cytokines (IL-6 and tumor necrosis factor alpha).
78	16895974	Using cells derived from TLR2-deficient mice and in vitro transfection assays, we demonstrated that this response was mediated by TLR2 and did not require the LPS-binding protein.
79	16895974	F. tularensis appeared to activate TLR2/TLR1 and TLR2/TLR6 heterodimers.
80	16895974	IL-1beta secretion, a reflection of caspase-1 activation, was induced by live but not heat-killed F. tularensis, despite the fact that both forms of the bacterium equally induced the IL-1beta transcript.
81	17202359	Using flow cytometry to assess TLR-induced cytokine production, we observed a substantial, highly significant defect in TLR1/2-induced TNF-alpha (p = 0.0003) and IL-6 (p < 0.0001) production, in older adults compared with young controls.
82	17202359	Production of IL-6 (p < 0.0001) and TNF-alpha (p = 0.003) after stimulation by N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2R,S)-propyl]-Cys-[S]-Ser1-[S]-Lys(4) trihydrochloride was strongly associated with TLR1 surface expression.
83	17549472	In the group with only one invaded lymph node, the estimated relapse rate was significantly lower (P (adjusted) = 0.0219) and the overall survival was increased (P (adjusted) = 0.0125) in the TIL+IL-2 arm compared with the IL-2 only arm.
84	17659370	ITAC-recruited TILs exhibited 4T1-specific proliferation and cytotoxicity, and an increased IFN-gamma but decreased IL-4 production.
85	17974999	CD8+ T cells specific for hTERT naturally occur in certain populations of cancer patients in remission, but it remains poorly understood whether such T cells could contribute to tumor immunosurveillance.
86	17974999	Tumor-infiltrating lymphocytes (TIL) were evident after, but not before vaccination, with 4% to 13% of postvaccine CD8+ TIL specific for the immunizing hTERT peptide.
87	17974999	Induction of TIL manifested clinically with tumor site pain and pruritus and pathologically with alterations in the tumor microenvironment, featuring histiocytic accumulation and widespread tumor necrosis. hTERT-specific CD8+ T cells were also evident after vaccination in the peripheral blood of patients and exhibited effector functions in vitro including proliferation, IFN-gamma production, and tumor lysis.
88	19082488	The chemotherapy resulted in the decrease of the CD4+ and CD8+ TIL, increase of the Gr-1+/CD11b+ TIL, no changes in the infiltration with CD4+/CD25+ Treg TIL, and decrease of the cytolytic and proliferative potential of the CD45+ TIL.
89	19082488	Subsequent immunotherapy with the IL-12-producing, genetically modified TC-1 (TC-1-IL-12) cells increased tumour infiltration with CD8+ and CD4+ cells, decreased the Gr-1+/CD11b+ cells, and increased the cytolytic and proliferative potential of the CD45+ TIL.
90	19793902	Mycoplasma genitalium-derived lipid-associated membrane proteins activate NF-kappaB through toll-like receptors 1, 2, and 6 and CD14 in a MyD88-dependent pathway.
91	19793902	However, the interaction of M. genitalium-derived LAMPs as pathogenic agents with Toll-like receptors (TLRs) and the signaling pathways responsible for active inflammation and NF-kappaB activation have not been fully elucidated.
92	19793902	In this study, LAMPs induced the production of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in a dose-dependent manner.
93	19793902	Blocking assays showed that TLR2- and CD14-neutralizing antibodies reduced the expression of TNF-alpha and IL-6 in THP-1 cells.
94	19793902	Furthermore, LAMP-induced NF-kappaB activation was increased in 293T cells transfected with TLR2 plasmid.
95	19793902	The activity of NF-kappaB was synergically augmented by cotransfected TLR1, TLR6, and CD14.
96	19793902	Additionally, LAMPs were shown to inhibit NF-kappaB expression by cotransfection with dominant-negative MyD88 and TLR2 plasmids.
97	19793902	These results suggest that M. genitalium-derived LAMPs activate NF-kappaB via TLR1, TLR2, TLR6, and CD14 in a MyD88-dependent pathway.
98	19793902	Mycoplasma genitalium-derived lipid-associated membrane proteins activate NF-kappaB through toll-like receptors 1, 2, and 6 and CD14 in a MyD88-dependent pathway.
99	19793902	However, the interaction of M. genitalium-derived LAMPs as pathogenic agents with Toll-like receptors (TLRs) and the signaling pathways responsible for active inflammation and NF-kappaB activation have not been fully elucidated.
100	19793902	In this study, LAMPs induced the production of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in a dose-dependent manner.
101	19793902	Blocking assays showed that TLR2- and CD14-neutralizing antibodies reduced the expression of TNF-alpha and IL-6 in THP-1 cells.
102	19793902	Furthermore, LAMP-induced NF-kappaB activation was increased in 293T cells transfected with TLR2 plasmid.
103	19793902	The activity of NF-kappaB was synergically augmented by cotransfected TLR1, TLR6, and CD14.
104	19793902	Additionally, LAMPs were shown to inhibit NF-kappaB expression by cotransfection with dominant-negative MyD88 and TLR2 plasmids.
105	19793902	These results suggest that M. genitalium-derived LAMPs activate NF-kappaB via TLR1, TLR2, TLR6, and CD14 in a MyD88-dependent pathway.
106	20504771	TLR2, in cooperation with either TLR1 or TLR6, mediates responses to a wide variety of microbial products as well as products of host tissue damage.
107	20504771	In an effort to understand the structural basis of TLR2 recognition and uncover novel TLR2 agonists, a synthetic chemical library of 24,000 compounds was screened using an IL-8-driven luciferase reporter in cells expressing these human receptors.
108	20504771	The screening yielded several novel TLR2-dependent activators that utilize TLR1, TLR6, or both as co-receptors.
109	20504771	TLR2, in cooperation with either TLR1 or TLR6, mediates responses to a wide variety of microbial products as well as products of host tissue damage.
110	20504771	In an effort to understand the structural basis of TLR2 recognition and uncover novel TLR2 agonists, a synthetic chemical library of 24,000 compounds was screened using an IL-8-driven luciferase reporter in cells expressing these human receptors.
111	20504771	The screening yielded several novel TLR2-dependent activators that utilize TLR1, TLR6, or both as co-receptors.
112	20719885	A galectin-3 ligand corrects the impaired function of human CD4 and CD8 tumor-infiltrating lymphocytes and favors tumor rejection in mice.
113	20719885	We strengthened this hypothesis here by showing that CD8(+) TIL treated with an anti-galectin-3 antibody had an increased IFN-γ secretion.
114	20719885	Importantly, we observed that not only CD8(+) TIL but also CD4(+) TIL treated with GCS-100 secreted more IFN-γ on ex vivo restimulation.
115	20719885	A galectin-3 ligand corrects the impaired function of human CD4 and CD8 tumor-infiltrating lymphocytes and favors tumor rejection in mice.
116	20719885	We strengthened this hypothesis here by showing that CD8(+) TIL treated with an anti-galectin-3 antibody had an increased IFN-γ secretion.
117	20719885	Importantly, we observed that not only CD8(+) TIL but also CD4(+) TIL treated with GCS-100 secreted more IFN-γ on ex vivo restimulation.
118	20808895	The synthetic bacterial lipopeptide Pam3-Cys-Ser-Lys4 (Pam3CSK4), the prototype ligand for the heterodimeric TLR1/TLR2 complex, enhanced RSV infection in primary epithelial, myeloid and lymphoid cells.
119	20809414	Dimerization between either of the two avian TLR2 species and TLR1La or 1Lb permits recognition of the same broad range of molecules as recognized by mammalian TLR2 dimerized with either TLR1, 6 and 10.
120	20809414	Components of downstream TLR signaling are also mostly conserved but with some losses in avian species; notably, TRAM is absent in avian genomes and, hence, the TRIF/TRAM-dependent signaling pathway utilized by mammals in LPS activation appears to be absent in birds.
121	21717068	The number of T-bet(+) TILs correlates with better survival of esophageal cancer patients.
122	21717068	Using well-defined mouse models, we have further shown that T-bet and Eomes are both required for the adaptive anti-tumor immunity by regulating T-cell trafficking into the tumor tissue and their effector functions inside the tumor microenvironment.
123	21717068	In order to gain further insight into the tumor immune microenvironment in the upper GI cancer, we have also studied expression levels of co-inhibitory molecules such as B7-H1/PD-L1 and B7-H4 in tissue specimens of esophageal and gastric cancers.
124	21717068	The number of CD3(+) and CD8(+) TILs correlates inversely with expression levels of B7-H4 in samples from esophageal cancer, supporting a role of active immune suppression by inhibitory B7 molecules in the tumor microenvironment.
125	21717068	In addition, TILs show functional exhaustion and express high levels of PD-1 and Tim-3.
126	21717068	Future tumor vaccine design should combine blockade of B7 inhibitory molecules and enhancement of T-bet and Eomes levels within the tumor microenvironment.
127	21717068	The number of T-bet(+) TILs correlates with better survival of esophageal cancer patients.
128	21717068	Using well-defined mouse models, we have further shown that T-bet and Eomes are both required for the adaptive anti-tumor immunity by regulating T-cell trafficking into the tumor tissue and their effector functions inside the tumor microenvironment.
129	21717068	In order to gain further insight into the tumor immune microenvironment in the upper GI cancer, we have also studied expression levels of co-inhibitory molecules such as B7-H1/PD-L1 and B7-H4 in tissue specimens of esophageal and gastric cancers.
130	21717068	The number of CD3(+) and CD8(+) TILs correlates inversely with expression levels of B7-H4 in samples from esophageal cancer, supporting a role of active immune suppression by inhibitory B7 molecules in the tumor microenvironment.
131	21717068	In addition, TILs show functional exhaustion and express high levels of PD-1 and Tim-3.
132	21717068	Future tumor vaccine design should combine blockade of B7 inhibitory molecules and enhancement of T-bet and Eomes levels within the tumor microenvironment.
133	21852947	Association of human TLR1 and TLR6 deficiency with altered immune responses to BCG vaccination in South African infants.
134	21852947	After stimulation with TLR1/6 lipopeptide ligands, PBMCs from TLR1/6-deficient individuals (stratified by TLR1_T1805G and TLR6_C745T hyporesponsive genotypes) secreted lower amounts of IL-6 and IL-10 compared to those with responsive TLR1/6 genotypes.
135	21852947	These data support a mechanism where TLR1/6 polymorphisms modulate TH1 T-cell polarization through genetic regulation of monocyte IL-10 secretion in the absence of IL-12.
136	21852947	Association of human TLR1 and TLR6 deficiency with altered immune responses to BCG vaccination in South African infants.
137	21852947	After stimulation with TLR1/6 lipopeptide ligands, PBMCs from TLR1/6-deficient individuals (stratified by TLR1_T1805G and TLR6_C745T hyporesponsive genotypes) secreted lower amounts of IL-6 and IL-10 compared to those with responsive TLR1/6 genotypes.
138	21852947	These data support a mechanism where TLR1/6 polymorphisms modulate TH1 T-cell polarization through genetic regulation of monocyte IL-10 secretion in the absence of IL-12.
139	21852947	Association of human TLR1 and TLR6 deficiency with altered immune responses to BCG vaccination in South African infants.
140	21852947	After stimulation with TLR1/6 lipopeptide ligands, PBMCs from TLR1/6-deficient individuals (stratified by TLR1_T1805G and TLR6_C745T hyporesponsive genotypes) secreted lower amounts of IL-6 and IL-10 compared to those with responsive TLR1/6 genotypes.
141	21852947	These data support a mechanism where TLR1/6 polymorphisms modulate TH1 T-cell polarization through genetic regulation of monocyte IL-10 secretion in the absence of IL-12.
142	22658914	We explored the associations of different genotypes of SLA class II and of the genes TLR1, TLR4, TLR5, and TLR6 with antibody responses after vaccination against Erysipelothrix rhusiopathiae (ER) and Actinobacillus pleuropneumoniae (APP) serotypes 1, 2, and 5 in 191 Duroc pigs maintained under specific pathogen-free conditions.
143	22658914	We demonstrated close relationships between SLA class II and ER antibody response and between TLR genes other than TLR4 and APP antibody responses.
144	23132491	Intracellular signaling pathways leading to host cell inflammation and innate immunity to Chlamydia include those mediated by Toll-like receptors (TLRs) and nucleotide binding oligomerization domain 1 (Nod1) protein.
145	23132491	There is evidence that TLR3, TLR4, and, particularly, TLR2 are critical for Chlamydia-mediated host cell activation and pathology.
146	23132491	Using MOMP formed in pure protein micelles (proteosomes), we show the induction of TLR2-dependent interleukin-8 (IL-8) and IL-6 secretion in vitro, the involvement of TLR1 as a TLR2 coreceptor, and the activation of both NF-κB and mitogen-activated protein (MAP) kinase intracellular pathways.
147	23610140	In this study, we investigated whether the effector function of CD8 TILs could be rescued by converting the chronic inflammation milieu to acute inflammation within tumors.
148	23610140	We found that injection of TLR3/9 ligands (polyI:C/CpG) into a tumor during the effector phase of lentivector (lv) immunization effectively rescued the function of lv-activated CD8 TILs and decreased the percentage of T regulatory within the tumor, resulting in a marked improvement in the antitumor efficacy of lv immunization.
149	23610140	Mechanistically, rescue of the effector function of CD8 TILs by TLR3/9 ligands is most likely dependent on production, within a tumor, of type-1 IFN that can mature and activate tumor-infiltrating dendritic cells.
150	23610140	The effector function of CD8 TILs could not be rescued in mice lacking intact type I IFN signaling.
151	23610140	These findings have important implications for tumor immunotherapy, suggesting that type I IFN-mediated activation of tumor-infiltrating dendritic cells within a tumor will most likely restore/enhance the effector function of CD8 TILs and thus improve the antitumor efficacy of current cancer vaccines.
152	23610140	In this study, we investigated whether the effector function of CD8 TILs could be rescued by converting the chronic inflammation milieu to acute inflammation within tumors.
153	23610140	We found that injection of TLR3/9 ligands (polyI:C/CpG) into a tumor during the effector phase of lentivector (lv) immunization effectively rescued the function of lv-activated CD8 TILs and decreased the percentage of T regulatory within the tumor, resulting in a marked improvement in the antitumor efficacy of lv immunization.
154	23610140	Mechanistically, rescue of the effector function of CD8 TILs by TLR3/9 ligands is most likely dependent on production, within a tumor, of type-1 IFN that can mature and activate tumor-infiltrating dendritic cells.
155	23610140	The effector function of CD8 TILs could not be rescued in mice lacking intact type I IFN signaling.
156	23610140	These findings have important implications for tumor immunotherapy, suggesting that type I IFN-mediated activation of tumor-infiltrating dendritic cells within a tumor will most likely restore/enhance the effector function of CD8 TILs and thus improve the antitumor efficacy of current cancer vaccines.
157	23610140	In this study, we investigated whether the effector function of CD8 TILs could be rescued by converting the chronic inflammation milieu to acute inflammation within tumors.
158	23610140	We found that injection of TLR3/9 ligands (polyI:C/CpG) into a tumor during the effector phase of lentivector (lv) immunization effectively rescued the function of lv-activated CD8 TILs and decreased the percentage of T regulatory within the tumor, resulting in a marked improvement in the antitumor efficacy of lv immunization.
159	23610140	Mechanistically, rescue of the effector function of CD8 TILs by TLR3/9 ligands is most likely dependent on production, within a tumor, of type-1 IFN that can mature and activate tumor-infiltrating dendritic cells.
160	23610140	The effector function of CD8 TILs could not be rescued in mice lacking intact type I IFN signaling.
161	23610140	These findings have important implications for tumor immunotherapy, suggesting that type I IFN-mediated activation of tumor-infiltrating dendritic cells within a tumor will most likely restore/enhance the effector function of CD8 TILs and thus improve the antitumor efficacy of current cancer vaccines.
162	23633484	Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors.
163	23633484	In this study, we document parallel regulation of CD8(+) T cells and Foxp3(+) Tregs by programmed death-1 (PD-1, PDCD1).
164	23633484	In addition, we identify an additional role of CTL antigen-4 (CTLA-4) inhibitory receptor in further promoting dysfunction of CD8(+) T effector cells in tumor models (CT26 colon carcinoma and ID8-VEGF ovarian carcinoma).
165	23633484	Two thirds of CD8(+) tumor-infiltrating lymphocytes (TIL) expressed PD-1, whereas one third to half of CD8(+) TIL coexpressed PD-1 and CTLA-4.
166	23633484	Double-positive (PD-1(+)CTLA-4(+)) CD8(+) TIL had characteristics of more severe dysfunction than single-positive (PD-1(+) or CTLA-4(+)) TIL, including an inability to proliferate and secrete effector cytokines.
167	23633484	Blockade of both PD-1 and CTLA-4 resulted in reversal of CD8(+) TIL dysfunction and led to tumor rejection in two thirds of mice.
168	23633484	Double blockade was associated with increased proliferation of antigen-specific effector CD8(+) and CD4(+) T cells, antigen-specific cytokine release, inhibition of suppressive functions of Tregs, and upregulation of key signaling molecules critical for T-cell function.
169	23633484	When used in combination with GVAX vaccination (consisting of granulocyte macrophage colony-stimulating factor-expressing irradiated tumor cells), inhibitory pathway blockade induced rejection of CT26 tumors in 100% of mice and ID8-VEGF tumors in 75% of mice.
170	23633484	Our study indicates that PD-1 signaling in tumors is required for both suppressing effector T cells and maintaining tumor Tregs, and that PD-1/PD-L1 pathway (CD274) blockade augments tumor inhibition by increasing effector T-cell activity, thereby attenuating Treg suppression.
171	23633484	Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors.
172	23633484	In this study, we document parallel regulation of CD8(+) T cells and Foxp3(+) Tregs by programmed death-1 (PD-1, PDCD1).
173	23633484	In addition, we identify an additional role of CTL antigen-4 (CTLA-4) inhibitory receptor in further promoting dysfunction of CD8(+) T effector cells in tumor models (CT26 colon carcinoma and ID8-VEGF ovarian carcinoma).
174	23633484	Two thirds of CD8(+) tumor-infiltrating lymphocytes (TIL) expressed PD-1, whereas one third to half of CD8(+) TIL coexpressed PD-1 and CTLA-4.
175	23633484	Double-positive (PD-1(+)CTLA-4(+)) CD8(+) TIL had characteristics of more severe dysfunction than single-positive (PD-1(+) or CTLA-4(+)) TIL, including an inability to proliferate and secrete effector cytokines.
176	23633484	Blockade of both PD-1 and CTLA-4 resulted in reversal of CD8(+) TIL dysfunction and led to tumor rejection in two thirds of mice.
177	23633484	Double blockade was associated with increased proliferation of antigen-specific effector CD8(+) and CD4(+) T cells, antigen-specific cytokine release, inhibition of suppressive functions of Tregs, and upregulation of key signaling molecules critical for T-cell function.
178	23633484	When used in combination with GVAX vaccination (consisting of granulocyte macrophage colony-stimulating factor-expressing irradiated tumor cells), inhibitory pathway blockade induced rejection of CT26 tumors in 100% of mice and ID8-VEGF tumors in 75% of mice.
179	23633484	Our study indicates that PD-1 signaling in tumors is required for both suppressing effector T cells and maintaining tumor Tregs, and that PD-1/PD-L1 pathway (CD274) blockade augments tumor inhibition by increasing effector T-cell activity, thereby attenuating Treg suppression.
180	23844129	Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders.
181	23844129	In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Rα two days post-vaccination can classify high and low responders with over 80% accuracy.
182	23844129	Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A.
183	23844129	Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders.
184	23844129	In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Rα two days post-vaccination can classify high and low responders with over 80% accuracy.
185	23844129	Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A.
186	24474335	Digital IHC was employed prevaccination and postvaccination to measure CD4 and CD8 TILs, as well as Treg TILs by conventional IHC.
187	24474335	Few correlations were observed with CD4, CD8 or Treg in TILs vs.
188	24474335	However, patients with lower levels of CD4 TILs prevaccination showed the greatest increases in CD4 TILs postvaccine, while Treg TILs decreased postvaccine.
189	24474335	There was also a strong correlation between decreases in serum PSA and increases in CD8 TILs postvaccine.
190	24474335	Digital IHC was employed prevaccination and postvaccination to measure CD4 and CD8 TILs, as well as Treg TILs by conventional IHC.
191	24474335	Few correlations were observed with CD4, CD8 or Treg in TILs vs.
192	24474335	However, patients with lower levels of CD4 TILs prevaccination showed the greatest increases in CD4 TILs postvaccine, while Treg TILs decreased postvaccine.
193	24474335	There was also a strong correlation between decreases in serum PSA and increases in CD8 TILs postvaccine.
194	24733845	Older infants displayed substantial activation of all three signal transduction molecules: degradation of NF-κB inhibitor IκBα and phosphorylation of MAPK Erk and p38 upon TLR1/2 triggering, compared with predominant activation of only one of any of these molecules in newborns.
195	24760892	Here we show that TLR2/6 but not TLR1/2 heterodimers sense Junín virus glycoprotein and induce a cytokine response, which in turn upregulates the expression of the RNA helicases RIG-I and MDA5.
196	24760892	NF-κB and Erk1/2 were important in the cytokine response, since both proteins were phosphorylated as a result of the interaction of virus with TLR2, and treatment with an Erk1/2-specific inhibitor blocked cytokine production.
197	25092771	Tumor vasculature was measured by immunohistochemistry using three endothelial cell markers: CD31 (mature), CD105 (immature/proliferating), and CD11b (monocytic).
198	25092771	This combination therapy also increased TILs, including tumor antigen-specific CD8 T cells, and elevated the expression of activation markers FAS-L, CXCL-9, CD31, and CD105 in MDSCs and TAMs, leading to reduced tumor volumes and an increase in the number of tumor-free animals.
199	25312698	Among the TLR family, TLR1, TLR2, TLR4, and TLR9 and their down-stream signaling proteins play critical roles in the initiation of the immune response in the pathogenesis of TB.
200	25312698	The inflammasome pathway is associated with the coordinated release of cytokines such as IL-1β and IL-18 which also play a role in the pathogenesis of TB.
201	25536171	B cell TLR1/2, TLR4, TLR7 and TLR9 interact in induction of class switch DNA recombination: modulation by BCR and CD40, and relevance to T-independent antibody responses.
202	25536171	Here, we have addressed cross-regulation between two different TLRs or between a TLR and CD40 in CSR induction by using a B cell stimulation system involving lipopolysaccharides (LPS).
203	25536171	Consistent with the requirement for dual TLR and BCR engagement in CSR induction, LPS, which engages TLR4 through its lipid A moiety, triggered cytosolic Ca2+ flux in B cells through its BCR-engaging polysaccharidic moiety.
204	25536171	In the presence of BCR crosslinking, LPS synergized with a TLR1/2 ligand (Pam3CSK4) in CSR induction, but much less efficiently with a TLR7 (R-848) or TLR9 (CpG) ligand.
205	25536171	In the absence of BCR crosslinking, R-848 and CpG, which per se induced marginal CSR, virtually abrogated CSR to IgG1, IgG2a, IgG2b, IgG3 and/or IgA, as induced by LPS or CD154 (CD40 ligand) plus IL-4, IFN-γ or TGF-β, and reduced secretion of class-switched Igs, without affecting B cell proliferation or IgM expression.
206	25536171	The CSR inhibition by TLR9 was associated with the reduction in AID expression and/or IgH germline IH-S-CH transcription, and required co-stimulation of B cells by CpG with LPS or CD154.
207	25536171	Unexpectedly, B cells also failed to undergo CSR or plasma cell differentiation when co-stimulated by LPS and CD154.
208	25536171	Overall, by addressing the interaction of TLR1/2, TLR4, TLR7 and TLR9 in the induction of CSR and modulation of TLR-dependent CSR by BCR and CD40, our study suggests the complexity of how different stimuli cross-regulate an important B cell differentiation process and an important role of TLRs in inducing effective T-independent antibody responses to microbial pathogens, allergens and vaccines.
209	25536171	B cell TLR1/2, TLR4, TLR7 and TLR9 interact in induction of class switch DNA recombination: modulation by BCR and CD40, and relevance to T-independent antibody responses.
210	25536171	Here, we have addressed cross-regulation between two different TLRs or between a TLR and CD40 in CSR induction by using a B cell stimulation system involving lipopolysaccharides (LPS).
211	25536171	Consistent with the requirement for dual TLR and BCR engagement in CSR induction, LPS, which engages TLR4 through its lipid A moiety, triggered cytosolic Ca2+ flux in B cells through its BCR-engaging polysaccharidic moiety.
212	25536171	In the presence of BCR crosslinking, LPS synergized with a TLR1/2 ligand (Pam3CSK4) in CSR induction, but much less efficiently with a TLR7 (R-848) or TLR9 (CpG) ligand.
213	25536171	In the absence of BCR crosslinking, R-848 and CpG, which per se induced marginal CSR, virtually abrogated CSR to IgG1, IgG2a, IgG2b, IgG3 and/or IgA, as induced by LPS or CD154 (CD40 ligand) plus IL-4, IFN-γ or TGF-β, and reduced secretion of class-switched Igs, without affecting B cell proliferation or IgM expression.
214	25536171	The CSR inhibition by TLR9 was associated with the reduction in AID expression and/or IgH germline IH-S-CH transcription, and required co-stimulation of B cells by CpG with LPS or CD154.
215	25536171	Unexpectedly, B cells also failed to undergo CSR or plasma cell differentiation when co-stimulated by LPS and CD154.
216	25536171	Overall, by addressing the interaction of TLR1/2, TLR4, TLR7 and TLR9 in the induction of CSR and modulation of TLR-dependent CSR by BCR and CD40, our study suggests the complexity of how different stimuli cross-regulate an important B cell differentiation process and an important role of TLRs in inducing effective T-independent antibody responses to microbial pathogens, allergens and vaccines.
217	25536171	B cell TLR1/2, TLR4, TLR7 and TLR9 interact in induction of class switch DNA recombination: modulation by BCR and CD40, and relevance to T-independent antibody responses.
218	25536171	Here, we have addressed cross-regulation between two different TLRs or between a TLR and CD40 in CSR induction by using a B cell stimulation system involving lipopolysaccharides (LPS).
219	25536171	Consistent with the requirement for dual TLR and BCR engagement in CSR induction, LPS, which engages TLR4 through its lipid A moiety, triggered cytosolic Ca2+ flux in B cells through its BCR-engaging polysaccharidic moiety.
220	25536171	In the presence of BCR crosslinking, LPS synergized with a TLR1/2 ligand (Pam3CSK4) in CSR induction, but much less efficiently with a TLR7 (R-848) or TLR9 (CpG) ligand.
221	25536171	In the absence of BCR crosslinking, R-848 and CpG, which per se induced marginal CSR, virtually abrogated CSR to IgG1, IgG2a, IgG2b, IgG3 and/or IgA, as induced by LPS or CD154 (CD40 ligand) plus IL-4, IFN-γ or TGF-β, and reduced secretion of class-switched Igs, without affecting B cell proliferation or IgM expression.
222	25536171	The CSR inhibition by TLR9 was associated with the reduction in AID expression and/or IgH germline IH-S-CH transcription, and required co-stimulation of B cells by CpG with LPS or CD154.
223	25536171	Unexpectedly, B cells also failed to undergo CSR or plasma cell differentiation when co-stimulated by LPS and CD154.
224	25536171	Overall, by addressing the interaction of TLR1/2, TLR4, TLR7 and TLR9 in the induction of CSR and modulation of TLR-dependent CSR by BCR and CD40, our study suggests the complexity of how different stimuli cross-regulate an important B cell differentiation process and an important role of TLRs in inducing effective T-independent antibody responses to microbial pathogens, allergens and vaccines.
225	25624476	In addition, it increased the number of CD8(+) tumor-infiltrating lymphocytes (TILs) and protected them from apoptosis and exhaustion characterized by decreased production of IL-2, TNFα, and IFNγ.
226	25624476	CD8(+) TILs capable of producing multiple cytokines were mainly PD-1(-)Tim-3(+), an effector memory subset responsible for tumor rejection.
227	25624476	Combined use of metformin and cancer vaccine improved CD8(+) TIL multifunctionality.
228	25624476	The adoptive transfer of antigen-specific CD8(+) T cells treated with metformin concentrations as low as 10 μM showed efficient migration into tumors while maintaining multifunctionality in a manner sensitive to the AMP-activated protein kinase (AMPK) inhibitor compound C.
229	25624476	In addition, it increased the number of CD8(+) tumor-infiltrating lymphocytes (TILs) and protected them from apoptosis and exhaustion characterized by decreased production of IL-2, TNFα, and IFNγ.
230	25624476	CD8(+) TILs capable of producing multiple cytokines were mainly PD-1(-)Tim-3(+), an effector memory subset responsible for tumor rejection.
231	25624476	Combined use of metformin and cancer vaccine improved CD8(+) TIL multifunctionality.
232	25624476	The adoptive transfer of antigen-specific CD8(+) T cells treated with metformin concentrations as low as 10 μM showed efficient migration into tumors while maintaining multifunctionality in a manner sensitive to the AMP-activated protein kinase (AMPK) inhibitor compound C.
233	25677543	Most genes showed increased expression (1) in the distal than in the proximal parts of the small intestine (TLR3, 5, RIG-I, IL-1β, IL-8, and IFN-γ); (2) in lymphoid organs (TLR1, 2, 6, 9, 10, IL-10, TNF-α), especially the MLN (TLR4, 7, 8, NOD1, NOD2, NALP3, IFN-α, IL-6, IL-12, and TGF-β), than in intestinal segments.
234	25677543	The analysis along the crypt/villus identified: (1) genes with higher expression in lamina propria (TLR1, 2, 4, 9, NOD1, NOD2, IL-1β, IL-10, TGF-β, TNF-α) and (2) genes with higher expression in the villus (TLR3, 5, 6, RIG-I, IL-6).
235	26101787	By binding to both TLR1 and TLR2, CU-T12-9 facilitates the TLR1/2 heterodimeric complex formation, which in turn activates the downstream signaling.
236	26101787	Fluorescence anisotropy assays revealed competitive binding to the TLR1/2 complex between CU-T12-9 and Pam₃CSK₄ with a half-maximal inhibitory concentration (IC₅₀) of 54.4 nM.
237	26101787	Finally, we showed that CU-T12-9 signals through nuclear factor κB (NF-κB) and invokes an elevation of the downstream effectors tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and inducible nitric oxide synthase (iNOS).
238	26101787	By binding to both TLR1 and TLR2, CU-T12-9 facilitates the TLR1/2 heterodimeric complex formation, which in turn activates the downstream signaling.
239	26101787	Fluorescence anisotropy assays revealed competitive binding to the TLR1/2 complex between CU-T12-9 and Pam₃CSK₄ with a half-maximal inhibitory concentration (IC₅₀) of 54.4 nM.
240	26101787	Finally, we showed that CU-T12-9 signals through nuclear factor κB (NF-κB) and invokes an elevation of the downstream effectors tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and inducible nitric oxide synthase (iNOS).
241	26148331	We observed that at d 3-4 post vaccination, 6 genes were down-regulated, namely APC, CD3G, FASLG, IL7, CD8A and TLR1.
242	26148331	Meanwhile at 6-7 days post vaccination, 9 genes were significantly up-regulated, including RIPK2, TGFB1, MICB, SOCS1, IL2RA, MS4A1, PTPRC, IL2 and IL8.
243	26148331	By days 12-15 the genes RIPK2, IL4, IL12B and TLR2 were overexpressed.
244	26303218	We have recently reported that Vi can generate inflammatory responses through activation of the TLR2/TLR1 complex.
245	26395101	In response to microbial pattern molecules, these DCs upgrade the maturation stage sufficient to improve cross-presentation of exogenous Ag, and upregulation of MHC and costimulators, allowing CD4/CD8 T cells to proliferate and liberating cytokines/chemokines that support lymphocyte attraction and survival.
246	26395101	Mouse CD8α(+) DCs express TLR7 and TLR9 in addition to the TLR2 family (TLR1, 2, and 6) and TLR3, whereas human CD141(+) DCs exclusively express the TLR2 family and TLR3.
247	26395101	In contrast, TLR2 and TLR3 are similarly expressed in both human and mouse Ag-presenting DCs.
248	26395101	Bacillus Calmette-Guerin peptidoglycan and polyinosinic-polycytidylic acid are representative agonists for TLR2 and TLR3, respectively, although they additionally stimulate cytoplasmic sensors: their functional specificities may not be limited to the relevant TLRs.
249	26395101	We herein summarize the history and perspectives of TLR2 and TLR3 agonists in vaccine-adjuvant immunotherapy for cancer.