Roth, StefanStefanRothCao, JiayuJiayuCaoSingh, VikramjeetVikramjeetSinghTiedt, SteffenSteffenTiedtHundeshagen, GabrielGabrielHundeshagenLi, TingTingLiBoehme, Julia D.Julia D.BoehmeChauhan, DhruvDhruvChauhanZhu, JieJieZhuRicci, AlessioAlessioRicciGorka, OliverOliverGorkaAsare, YawYawAsareYang, JunJunYangLopez, Mary S.Mary S.LopezRehberg, MarkusMarkusRehbergBruder, DunjaDunjaBruderZhang, ShengxiangShengxiangZhangGroß, OlafOlafGroßDichgans, MartinMartinDichgansHornung, VeitVeitHornungLiesz, ArthurArthurLiesz2022-08-182022-08-182021https://resolver.sub.uni-goettingen.de/purl?gro-2/113007Loss of lymphocytes, particularly T cell apoptosis, is a central pathological event after severe tissue injury that is associated with increased susceptibility for life-threatening infections. The precise immunological mechanisms leading to T cell death after acute injury are largely unknown. Here, we identified a monocyte-T cell interaction driving bystander cell death of T cells in ischemic stroke and burn injury. Specifically, we found that stroke induced a FasL-expressing monocyte population, which led to extrinsic T cell apoptosis. This phenomenon was driven by AIM2 inflammasome-dependent interleukin-1β (IL-1β) secretion after sensing cell-free DNA. Pharmacological inhibition of this pathway improved T cell survival and reduced post-stroke bacterial infections. As such, this study describes inflammasome-dependent monocyte activation as a previously unstudied cause of T cell death after injury and challenges the current paradigms of post-injury lymphopenia.enjournal_article10.1016/j.immuni.2021.02.00433667383