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, Kenya Honda, Koji Atarashi, Fukiko Kobayashi, Takashi Ebihara, Hiroyuki Oshiumi, Misako Matsumoto, Masashi Shingai, Tsukasa Seya

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)100-110
Number of pages11
JournalMolecular Immunology
Volume57
Issue number2
DOIs
Publication statusPublished - 2014 Feb

Keywords

  • Dendritic cells
  • Innate immunity
  • Measles virus
  • Mitochondrial antiviral signaling protein (MAVS)
  • Type I interferon

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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