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MAVS-dependent IRF3/7 bypass of interferon p-induction restricts the response to measles infection in CD150Tg mouse bone marrow-derived dendritic cells
Title: | MAVS-dependent IRF3/7 bypass of interferon p-induction restricts the response to measles infection in CD150Tg mouse bone marrow-derived dendritic cells |
Authors: | Takaki, Hiromi Browse this author | Honda, Kenya Browse this author | Atarashi, Koji Browse this author | Kobayashi, Fukiko Browse this author | Ebihara, Takashi Browse this author | Oshiumi, Hiroyuki Browse this author →KAKEN DB | Matsumoto, Misako Browse this author →KAKEN DB | Shingai, Masashi Browse this author | Seya, Tsukasa Browse this author →KAKEN DB |
Keywords: | Innate immunity | Dendritic cells | Type I interferon | Mitochondrial antiviral signaling protein (MAVS) | Measles virus |
Issue Date: | Feb-2014 |
Publisher: | Pergamon-elsevier science ltd |
Journal Title: | Molecular immunology |
Volume: | 57 |
Issue: | 2 |
Start Page: | 100 |
End Page: | 109 |
Publisher DOI: | 10.1016/j.molimm.2013.08.007 |
PMID: | 24096085 |
Abstract: | Measles virus (MV) infects CD150Tg/ifnar (IFN alpha receptor)(-/-) mice but not CD150 (a human MV receptor)-transgenic (Tg) mice. We have shown that bone marrow-derived dendritic cells (BMDCs) from CD150Tg/Ifnar(-/-) mice are permissive to MV in contrast to those from simple CD150Tg mice, which reveals a crucial role of type I interferon (IFN) in natural tropism against MV. Yet, the mechanism whereby BMDCs produce initial type I IFN has not been elucidated in MV infection. RNA virus infection usually allows cells to generate double-stranded RNA and induce activation of IFN regulatory factor (IRF) 3/7 transcription factors, leading to the production of type I IFN through the retinoic acid-inducible gene I (RIG-I)/melanoma differentiation-associated gene 5 (MDA5)-mitochondrial antiviral signaling protein (MAVS) pathway. In mouse experimental BMDCs models, we found CD150Tg/Mavs(-/-)BMDCs, but not CD150Tg/Irf3(-/-)/Irf7-/-BMDCs, permissive to MV. IFN-alpha/beta were not induced in MV-infected CD150Tg/Mavs--/-BMDCs, while IFN-13 was subtly induced in CD150Tg/Irf3(-/-)/Irf7(-/-)BMDCs. In vivo systemic infection was therefore established by transfer of MV-infected CD150Tg/Mavs-/- BMDCs to CD150Tg//fnar-/- mice. These data indicate that MAVS-dependent, IRF3/7-independent IFN-13 induction triggers the activation of the IFNAR pathway so as to restrict the spread of MV by infected BMDCs. Hence, MAVS participates in the initial induction of type I IFN in BMDCs and IFNAR protects against MV spreading. We also showed the importance of IL-10-producing CD4+ T cells induced by MV-infected BMDCs in vitro, which may account for immune modulation due to the functional aberration of DCs. (C) 2013 Elsevier Ltd. All rights reserved. |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/54683 |
Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 瀬谷 司
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