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

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.

• Authors: Hiromi Takaki, Kenya Honda, Koji Atarashi, Fukiko Kobayashi, Takashi Ebihara, Hiroyuki Oshiumi, Misako Matsumoto, Masashi Shingai, Tsukasa Seya
• Journal: Molecular immunology (Mol Immunol) Vol. 57 Issue 2 Pg. 100-10 (Feb 2014) ISSN: 1872-9142 [Electronic] England
• PMID: 24096085 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Adaptor Proteins, Signal Transducing
• Adaptor Proteins, Vesicular Transport
• Antigens, CD
• IPS-1 protein, mouse
• Interferon Regulatory Factor-3
• Interferon Regulatory Factor-7
• Irf7 protein, mouse
• Receptors, Cell Surface
• SLAMF1 protein, human
• TICAM-1 protein, mouse
• Interleukin-10
• Receptor, Interferon alpha-beta
• Signaling Lymphocytic Activation Molecule Family Member 1
• Interferon-beta
• Ddx58 protein, mouse
• Ifih1 protein, mouse
• DEAD Box Protein 58
• DEAD-box RNA Helicases
• Interferon-Induced Helicase, IFIH1

Topics

• Adaptor Proteins, Signal Transducing (deficiency, genetics, metabolism)
• Adaptor Proteins, Vesicular Transport (deficiency, genetics)
• Animals
• Antigens, CD (metabolism)
• Bone Marrow Cells (cytology)
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• Cell Line
• Chlorocebus aethiops
• DEAD Box Protein 58
• DEAD-box RNA Helicases (metabolism)
• Dendritic Cells (cytology, immunology)
• Interferon Regulatory Factor-3 (deficiency, genetics, metabolism)
• Interferon Regulatory Factor-7 (deficiency, genetics, metabolism)
• Interferon-Induced Helicase, IFIH1
• Interferon-beta (biosynthesis, metabolism)
• Interleukin-10 (metabolism)
• Measles (immunology)
• Measles virus (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Receptor, Interferon alpha-beta (genetics)
• Receptors, Cell Surface (metabolism)
• Signal Transduction (immunology)
• Signaling Lymphocytic Activation Molecule Family Member 1
• Vero Cells