2016 Fiscal Year Annual Research Report
The alarmin IL-33 derived from HSV-2-infected keratinocytes triggers mast cell-mediated antiviral innate immunity
| Project/Area Number |
26293256
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| Research Institution | University of Yamanashi |
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Principal Investigator |
島田 眞路 山梨大学, その他部局等, 学長 (10114505)
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| Co-Investigator(Kenkyū-buntansha) |
川村 龍吉 山梨大学, 総合研究部, 准教授 (70262657)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | IL-33 / herpes simplex virus / mast cell / innate immunity |
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| Outline of Annual Research Achievements |
IL-33, known as an “alarmin”, has shown protective effects against infections with some pathogens in various organs, however, its contribution to antiviral host defense in skin remains to be defined. Here, we found that, in herpes simplex virus (HSV)-2-infected murine skin, IL-33 protein kinetics paralleled the kinetics of HSV titer, suggesting that productive viral replication promotes IL-33 release in skin. Ex vivo mast cell (MC) activation analysis demonstrated that supernatants of HSV-2-infected epidermis of wild type (WT) mice, but not IL-33-/- mice, induced TNF-αproduction by bone marrow-derived MCs (BMMCs), indicating that IL-33 released from HSV-2-infected epidermis activates BMMCs. Moreover, ST2-/- mice exhibited increased clinical severity and mortality following cutaneous HSV-2 infection. To see whether IL-33/ST2 signaling on MCs contributes to antiviral host defense, bone marrow-derived mast cells (BMMCs) generated from WT or ST2-/- mice were reconstituted in the skin of MCs deficient (W/Wv) mice before HSV-2 infection. We found that intradermal reconstitution with WT-BMMCs, but not ST2-/- BMMCs, significantly restored the clinical severity and mortality in HSV-2-infected W/Wv mice, indicating the importance of IL-33/ST2 axis on MCs in host defense. Thus, IL-33 derived from epidermis damaged by HSV infection has a critical role in triggering MC-mediated antiviral responses.
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| Research Progress Status |
28年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
28年度が最終年度であるため、記入しない。
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| Causes of Carryover |
28年度が最終年度であるため、記入しない。
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| Expenditure Plan for Carryover Budget |
28年度が最終年度であるため、記入しない。
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