Impaired cross-presentation of CD8α+ CD11c+ dendritic cells by Japanese encephalitis virus in a TLR2/MyD88 signal pathway-dependent manner.
Cross-presentation is the pathway by which exogenous antigens are routed for presentation by MHC class I molecules leading to activation of antiviral CD8(+)  T-cell responses. However, there is little information describing the modulation of cross-presentation and the impact of pathogen-derived signals associated with Japanese encephalitis virus (JEV), which is one of the most common causes of encephalitis in humans. In this study, we demonstrate that JEV infection could suppress in vivo cross-presentation of soluble and cell-associated antigens, thereby generating weak CD8(+)  T-cell responses to exogenous antigens, as evaluated by CFSE dilution of adoptively transferred CD8(+)  T cells and in vivo CTL killing activity. Furthermore, CD8α(+) CD11c(+)  dendritic cells (DCs), which are known to be far more efficient at cross-presenting soluble antigens, played a specific role in contributing to JEV-mediated inhibition of the cross-presentation of exogenous antigens through interference with effective antigen uptake. Finally, this study provides evidence that TLR2-MyD88 and p38 MAPK signal pathway might be involved in JEV-mediated inhibition of cross-presentation of soluble and cell-associated antigens. These observations suggest that the modulation of cross-presentation of exogenous antigens through TLR signaling has important implications for antiviral immune responses against JEV infection and the development of effective vaccination strategies.
College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Jeonju, Republic of Korea.
Abi G
AG
Aleyas
Young Woo
YW
Han
Ajit Mahadev
AM
Patil
Seong Bum
SB
Kim
Koanhoi
K
Kim
Seong Kug
SK
Eo
D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D045142:Cross-Priming; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D004664:Encephalitis Virus, Japanese / Q000276:immunology*; D004672:Encephalitis, Japanese / Q000276:immunology*; D008213:Lymphocyte Activation; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
D000956:Antigens, Viral; D039521:CD11c Antigen; D016827:CD8 Antigens; C431698:CD8alpha antigen; D008565:Membrane Proteins; D053594:Myeloid Differentiation Factor 88; D051195:Toll-Like Receptor 2