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

Roth, Stefan; Cao, Jiayu; Singh, Vikramjeet; Tiedt, Steffen; Hundeshagen, Gabriel; Li, Ting; Boehme, Julia D.; Chauhan, Dhruv; Zhu, Jie; Ricci, Alessio; Gorka, Oliver; Asare, Yaw; Yang, Jun; Lopez, Mary S.; Rehberg, Markus; Bruder, Dunja; Zhang, Shengxiang; Gross, Olaf; Dichgans, Martin; Hornung, Veit und Liesz, Arthur (2021): Post-injury immunosuppression and secondary infections are caused by an AIM2 inflammasome-driven signaling cascade. In: Immunity, Bd. 54, Nr. 4: S. 648-659

Abstract

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-1 beta (IL-1 beta) 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1074-7613
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198