Functional modulation of dendritic cells and macrophages by Japanese encephalitis virus through MyD88 adaptor molecule-dependent and -independent pathways

J Immunol. 2009 Aug 15;183(4):2462-74. doi: 10.4049/jimmunol.0801952. Epub 2009 Jul 27.

Abstract

Dendritic cells (DCs) are potent initiators of T cell-mediated immunity that undergo maturation during viral infections. However, few reports describing the interactions of DCs with Japanese encephalitis virus (JEV), which remains the most frequent cause of acute and epidemic viral encephalitis, are available. In this study, we investigated the interaction of JEV with DCs and macrophages. JEV replicated its viral RNA in both cells with different efficiency, and JEV infection of macrophages followed the classical activation pathway of up-regulation of tested costimulatory molecules and proinflammatory cytokine production (IL-6, TNF-alpha, and IL-12). On the contrary, JEV-infected DCs failed to up-regulate costimulatory molecules such as CD40 and MHC class II. Of more interest, along with production of proinflammatory cytokines, DCs infected by JEV released antiinflammatory cytokine IL-10, which was not detected in macrophages. Moreover, signaling through MyD88 molecule, a pan-adaptor molecule of TLRs, and p38 MAPK in JEV-infected DCs was found to play a role in the production of cytokines and subversion of primary CD4(+) and CD8(+) T cell responses. We also found that IL-10 released from JEV-infected DCs led to a reduction in the priming of CD8(+) T cells, but not CD4(+) T cells. Taken together, our data suggest that JEV induces functional impairment of DCs through MyD88-dependent and -independent pathways, which subsequently leads to poor CD4(+) and CD8(+) T cell responses, resulting in boosting viral survival and dissemination in the body.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / virology
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology*
  • Encephalitis Virus, Japanese / immunology*
  • Encephalitis, Japanese / immunology
  • Encephalitis, Japanese / pathology
  • Encephalitis, Japanese / virology
  • Macrophage Activation / immunology
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / virology*
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Myeloid Differentiation Factor 88 / physiology*
  • Signal Transduction / immunology*
  • Virus Replication / immunology

Substances

  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88