{Reference Type}: Journal Article
{Title}: Type I interferon governs immunometabolic checkpoints that coordinate inflammation during Staphylococcal infection.
{Author}: Reynolds MB;Klein B;McFadden MJ;Judge NK;Navarrete HE;Michmerhuizen BC;Awad D;Schultz TL;Harms PW;Zhang L;O'Meara TR;Sexton JZ;Lyssiotis CA;Kahlenberg JM;O'Riordan MX;
{Journal}: Cell Rep
{Volume}: 43
{Issue}: 8
{Year}: 2024 Aug 27
暂无{DOI}: 10.1016/j.celrep.2024.114607
{Abstract}: Macrophage metabolic plasticity is central to inflammatory programming, yet mechanisms of coordinating metabolic and inflammatory programs during infection are poorly defined. Here, we show that type I interferon (IFN) temporally guides metabolic control of inflammation during methicillin-resistant Staphylococcus aureus (MRSA) infection. We find that staggered Toll-like receptor and type I IFN signaling in macrophages permit a transient energetic state of combined oxidative phosphorylation (OXPHOS) and aerobic glycolysis followed by inducible nitric oxide synthase (iNOS)-mediated OXPHOS disruption. This disruption promotes type I IFN, suppressing other pro-inflammatory cytokines, notably interleukin-1β. Upon infection, iNOS expression peaks at 24 h, followed by lactate-driven Nos2 repression via histone lactylation. Type I IFN pre-conditioning prolongs infection-induced iNOS expression, amplifying type I IFN. Cutaneous MRSA infection in mice constitutively expressing epidermal type I IFN results in elevated iNOS levels, impaired wound healing, vasculopathy, and lung infection. Thus, kinetically regulated type I IFN signaling coordinates immunometabolic checkpoints that control infection-induced inflammation.