Post-injury immunosuppression and secondary infections are caused by an AIM2 inflammasome-driven signaling cascade

Summary Loss of lymphocytes, particularly T cell apoptosis, is a central pathological event after severe tissue injury that associated with increased susceptibility for life-threatening infections. The precise immunological mechanisms leading to death acute are largely unknown. Here, we identified monocyte-T interaction driving bystander cells in ischemic stroke and burn injury. Specifically, found induced FasL-expressing monocyte population, which led extrinsic apoptosis. This phenomenon was driven by AIM2 inflammasome-dependent interleukin-1β (IL-1β) secretion sensing cell-free DNA. Pharmacological inhibition this pathway improved survival reduced post-stroke bacterial As such, study describes activation as previously unstudied cause challenges the current paradigms post-injury lymphopenia.