| First Author | Sin WX | Year | 2020 |
| Journal | Front Immunol | Volume | 11 |
| Pages | 640 | PubMed ID | 32373120 |
| Mgi Jnum | J:303146 | Mgi Id | MGI:6511434 |
| Doi | 10.3389/fimmu.2020.00640 | Citation | Sin WX, et al. (2020) IRF-7 Mediates Type I IFN Responses in Endotoxin-Challenged Mice. Front Immunol 11:640 |
| abstractText | 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-beta production in the TLR4 pathway. Here, we show that IRF-7 is essential for both type I IFN induction and IL-1beta responses via TLR4 in mice. Mice lacking Irf7 were defective in production of both IFN-beta and IL-1beta, an IFN-beta-induced pro-inflammatory cytokine, after LPS challenge. IFN-beta 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-beta 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-1beta production in mice. |
