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

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,...

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Main Authors: Roth, Stefan (Author) , Cao, Jiayu (Author) , Singh, Vikramjeet (Author) , Tiedt, Steffen (Author) , Hundeshagen, Gabriel (Author) , Li, Ting (Author) , Boehme, Julia D. (Author) , Chauhan, Dhruv (Author) , Zhu, Jie (Author) , Ricci, Alessio (Author) , Gorka, Oliver (Author) , Asare, Yaw (Author) , Yang, Jun (Author) , Lopez, Mary S. (Author) , Rehberg, Markus (Author) , Bruder, Dunja (Author) , Zhang, Shengxiang (Author) , Groß, Olaf (Author) , Dichgans, Martin (Author) , Hornung, Veit (Author) , Liesz, Arthur (Author)
Format: Article (Journal)
Language:English
Published: 4 March 2021
In: Immunity
Year: 2021, Volume: 54, Issue: 4, Pages: 648-659.e8
ISSN:1097-4180
DOI:10.1016/j.immuni.2021.02.004
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.immuni.2021.02.004
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1074761321000704
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Author Notes:Stefan Roth, Jiayu Cao, Vikramjeet Singh, Steffen Tiedt, Gabriel Hundeshagen, Ting Li, Julia D. Boehme, Dhruv Chauhan, Jie Zhu, Alessio Ricci, Oliver Gorka, Yaw Asare, Jun Yang, Mary S. Lopez, Markus Rehberg, Dunja Bruder, Shengxiang Zhang, Olaf Groß, Martin Dichgans, Veit Hornung, and Arthur Liesz
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Summary: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.
Item Description:Gesehen am 08.06.2021
Physical Description:Online Resource
ISSN:1097-4180
DOI:10.1016/j.immuni.2021.02.004

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