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* Laboratory of Microbiology, College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Jeonju, Republic of Korea;
College of Pharmacy, Chungbuk National University, Cheonju, Republic of Korea;
Immunomodulation Research Center, University of Ulsan, Ulsan, Republic of Korea; and
Department of Pharmacology, School of Medicine, Pusan National University, Busan, Republic of Korea
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-
, 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.
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1 This work was supported by Grant RTI05-03-02 from the Regional Technology Innovation Program of the Ministry of Commerce, Industry, and Energy (MOCIE), a research grant from the Bio-Safety Research Institute, Chonbuk National University, and by the Brain Korea 21 Project in 2008, Republic of Korea.
2 J.A.G. and Y.W.H. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Seong Kug Eo, Laboratory of Microbiology, College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Jeonju City 561-756, Republic of Korea. E-mail address: vetvirus{at}chonbuk.ac.kr
4 Abbreviations used in this paper: DC, dendritic cell; bmDC, bone marrow-derived DC; bmM
, bone marrow-derived macrophage; gB, glycoprotein B; JEV, Japanese encephalitis virus; MFI, mean fluorescence intensity; NS1, nonstructural protein 1; p.i., postinfection; TCID50, 50% tissue culture-infective dose.
5 The online version of this article contains supplemental material.
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