Toll-like receptor ligands induce expression of the costimulatory molecule CD155 on antigen-presenting cells.
Genotoxic stress and RAS induce the expression of CD155, a ligand for the immune receptors DNAM-1, CD96 and TIGIT. Here we show that antigen-presenting cells upregulate CD155 expression in response to Toll-like receptor activation. Induction of CD155 by Toll-like receptors depended on MYD88, TRIF and NF-κB. In addition, IRF3, but not IRF7, modulated CD155 upregulation in response to TLR3 signals. Immunization of CD155-deficient mice with OVA and the TLR9 agonist CpG resulted in increased OVA-specific IgG2a/c titers when compared to wild type mice. Splenocytes of immunized CD155-deficient mice secreted lower levels of IL-4 and fewer IL-4 and GATA-3 expressing CD4(+) T cells were present in the spleen of Cd155(-/-) mice. Our data suggest that CD155 regulates T(h)2 differentiation. Targeting of CD155 in immunization protocols using peptides may represent a promising new approach to boost protective humoral immunity in viral vaccines.
Immunology Programme, Department of Microbiology, National University of Singapore, Singapore, Singapore.
Neha
N
Kamran
Yoshimi
Y
Takai
Jun
J
Miyoshi
Subhra K
SK
Biswas
Justin S B
JS
Wong
Stephan
S
Gasser
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D004249:DNA Damage; D050990:GATA3 Transcription Factor / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D056724:Immunity, Humoral / Q000235:genetics; D008024:Ligands; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics* / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology / Q000378:metabolism; D000098862:T Lineage-Specific Activation Antigen 1
D033942:Adaptor Proteins, Vesicular Transport; D000945:Antigens, Differentiation, T-Lymphocyte; D050990:GATA3 Transcription Factor; D008024:Ligands; D053594:Myeloid Differentiation Factor 88; D011991:Receptors, Virus; D051196:Toll-Like Receptor 3; D014765:Viral Vaccines; D000098862:T Lineage-Specific Activation Antigen 1; C494748:Gata3 protein, mouse; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse; C519703:TLR3 protein, mouse; C066100:poliovirus receptor