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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
Roth, Stefan
Cao, Jiayu
Singh, Vikramjeet
Tiedt, Steffen
Hundeshagen, Gabriel
Li, Ting
Boehme, Julia D
Chauhan, Dhruv
Zhu, Jie
Ricci, Alessio
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2021-03-04
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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.
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Immunity. 2021 Apr 13;54(4):648-659.e8. doi: 10.1016/j.immuni.2021.02.004. Epub 2021 Mar 4.
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en
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1097-4180
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Attribution-NonCommercial-NoDerivatives 4.0 International