Loss 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.

淋巴细胞的丢失，尤其是 T 细胞凋亡，是严重组织损伤后的一个主要病理事件，与危及生命的感染的易感性增加有关。导致急性损伤后 T 细胞死亡的精确免疫机制在很大程度上是未知的。在这里，我们确定了一种单核细胞-T 细胞相互作用，导致缺血性中风和烧伤中 T 细胞的旁观者细胞死亡。具体而言，我们发现中风会诱导表达 FasL 的单核细胞群，从而导致外源性 T 细胞凋亡。这种现象是由检测无细胞 DNA 后 AIM2 炎症小体依赖性白细胞介素-1β（IL-1β）分泌所驱动的。该途径的药理学抑制改善了 T 细胞存活并减少了中风后细菌感染。像这样，