Cytolytic effector pathways and IFN-γ help protect against Japanese encephalitis

Maximilian Larena, Matthias Regner, Mario Lobigs*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    46 Citations (Scopus)

    Abstract

    Japanese encephalitis, caused by infection with the neurotropic flavivirus, Japanese encephalitis virus (JEV), is among the most important viral encephalitides in Asia. While previous studies established an essential role of Ab and type I IFN, it is still unclear if the cell-mediated immune responses, through their direct antiviral effector functions, contribute to protection against the fatal disease. We report here that mice defective in both the granule exocytosis and death receptor pathways of cytotoxicity display increased susceptibility to JEV. The two cell contact-dependent cytotoxic effector mechanisms act redundantly within the CNS to reduce disease severity. We also demonstrate that IFN-γ is critical in recovery from primary infection with JEV by a mechanism involving suppression of virus growth in the CNS, and that T cells are the main source of the cytokine that promotes viral clearance from the brain. Finally, we show by in vivo depletion of NK cells that this innate immune cell population is dispensable for control of JEV infection in the periphery and in the CNS. Accordingly, cell contact-dependent cytolytic and IFN-γ-dependent noncytolytic clearance of virus mediated by T cells trafficking into the CNS help in recovery from lethal infection in a mouse model of Japanese encephalitis.

    Original languageEnglish
    Pages (from-to)1789-1798
    Number of pages10
    JournalEuropean Journal of Immunology
    Volume43
    Issue number7
    DOIs
    Publication statusPublished - Jul 2013

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