RRC ID 58944
Author Sin WX, Yeong JP, Lim TJF, Su IH, Connolly JE, Chin KC.
Title IRF-7 Mediates Type I IFN Responses in Endotoxin-Challenged Mice.
Journal Front Immunol
Abstract IRF-7 mediates robust production of type I IFN via MyD88 of the TLR9 pathway in plasmacytoid dendritic cells (pDCs). Previous in vitro studies using bone marrow-derived dendritic cells lacking either Irf7 or Irf3 have demonstrated that only IRF-3 is required for IFN-β production in the TLR4 pathway. Here, we show that IRF-7 is essential for both type I IFN induction and IL-1β responses via TLR4 in mice. Mice lacking Irf7 were defective in production of both IFN-β and IL-1β, an IFN-β-induced pro-inflammatory cytokine, after LPS challenge. IFN-β production in response to LPS was impaired in IRF-7-deficient macrophages, but not dendritic cells. Unlike pDCs, IRF-7 is activated by the TRIF-, but not MyD88-, dependent pathway via TBK-1 in macrophages after LPS stimulation. Like pDCs, resting macrophages constitutively expressed IRF-7 protein. This basal IRF-7 protein was completely abolished in either Ifnar1-/- or Stat1-/- macrophages, which corresponded with the loss of LPS-stimulated IFN-β induction in these macrophages. These findings demonstrate that macrophage IRF-7 is critical for LPS-induced type I IFN responses, which in turn facilitate IL-1β production in mice.
Volume 11
Pages 640
Published 2020-4-16
DOI 10.3389/fimmu.2020.00640
PMID 32373120
PMC PMC7176903
MeSH Adaptor Proteins, Vesicular Transport / genetics Adaptor Proteins, Vesicular Transport / metabolism* Animals Cells, Cultured Dendritic Cells / immunology* Disease Models, Animal Endotoxemia / immunology* Endotoxins / immunology Humans Interferon Regulatory Factor-7 / genetics Interferon Regulatory Factor-7 / metabolism* Interferon Type I / metabolism* Interleukin-1beta / metabolism Macrophages / immunology* Mice Mice, Knockout Myeloid Differentiation Factor 88 / genetics Myeloid Differentiation Factor 88 / metabolism* Receptor, Interferon alpha-beta / genetics STAT1 Transcription Factor / genetics
IF 5.085
Times Cited 0
Mice RBRC00858 RBRC01420