This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.01640-07v1 82/1/196    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jung, A. Articles by Akira, S. Search for Related Content PubMed PubMed Citation Articles by Jung, A. Articles by Akira, S.

Lymphocytoid Choriomeningitis Virus Activates Plasmacytoid Dendritic Cells and Induces a Cytotoxic T-Cell Response via MyD88

Research Institute for Microbial Diseases, Department of Host Defense, Osaka University, Osaka, Japan,¹ Department of Neonatology, Campus Mitte, Charité-Universitaetsmedizin Berlin, Berlin, Germany,² ERATO, Japan Science and Technology Agency, Osaka, Japan³

Received 26 July 2007/ Accepted 4 October 2007

Toll-like receptors (TLRs) and retinoic acid-inducible gene I-like helicases (RLHs) are two major machineries recognizing RNA virus infection of innate immune cells. Intracellular signaling for TLRs and RLHs is mediated by their cytoplasmic adaptors, i.e., MyD88 or TRIF and IPS-1, respectively. In the present study, we investigated the contributions of TLRs and RLHs to the cytotoxic T-lymphocyte (CTL) response by using lymphocytoid choriomeningitis virus (LCMV) as a model virus. The generation of virus-specific cytotoxic T lymphocytes was critically dependent on MyD88 but not on IPS-1. Type I interferons (IFNs) are known to be important for the development of the CTL response to LCMV infection. Serum levels of type I IFNs and proinflammatory cytokines were mainly dependent on the presence of MyD88, although IPS-1^–/– mice showed a decrease in IFN- levels but not in IFN-β and proinflammatory cytokine levels. Analysis of Ifna6^+/GFP reporter mice revealed that plasmacytoid dendritic cells (DCs) are the major source of IFN- in LCMV infection. MyD88^–/– mice were highly susceptible to LCMV infection in vivo. These results suggest that recognition of LCMV by plasmacytoid DCs via TLRs is responsible for the production of type I IFNs in vivo. Furthermore, the activation of a MyD88-dependent innate mechanism induces a CTL response, which eventually leads to virus elimination.

Published ahead of print on 17 October 2007.

This article has been cited by other articles:

• Saito, T., Gale, M. Jr. (2008). Differential recognition of double-stranded RNA by RIG-I-like receptors in antiviral immunity. J. Exp. Med. 205: 1523-1527 [Abstract] [Full Text]