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. 2014 Feb;57(2):100-10.
doi: 10.1016/j.molimm.2013.08.007. Epub 2013 Oct 4.

MAVS-dependent IRF3/7 bypass of interferon β-induction restricts the response to measles infection in CD150Tg mouse bone marrow-derived dendritic cells

Hiromi Takaki  1 , Kenya Honda, Koji Atarashi, Fukiko Kobayashi, Takashi Ebihara, Hiroyuki Oshiumi, Misako Matsumoto, Masashi Shingai, Tsukasa Seya
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Free article

MAVS-dependent IRF3/7 bypass of interferon β-induction restricts the response to measles infection in CD150Tg mouse bone marrow-derived dendritic cells

Hiromi Takaki et al. Mol Immunol. 2014 Feb.
Free article

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-α/β were not induced in MV-infected CD150Tg/Mavs(-/-)BMDCs, while IFN-β 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/Ifnar(-/-) mice. These data indicate that MAVS-dependent, IRF3/7-independent IFN-β 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.

Keywords: BM; Dendritic cells; Innate immunity; MAVS; MDA5; MV; Measles virus; Mitochondrial antiviral signaling protein (MAVS); RIG-I; TICAM1; Toll/IL-1 receptor homology domain-containing adaptor molecule 1; Type I interferon; WT; bone marrow; measles virus; melanoma differentiation associated gene 5; mitochondrial antiviral signaling protein; retinoic acid inducible gene-I; wild-type.

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