Post-injury immunosuppression and secondary infections are caused by an AIM2 inflammasome-driven signaling cascade
2021 | journal article; research paper
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Post-injury immunosuppression and secondary infections are caused by an AIM2 inflammasome-driven signaling cascade
Roth, S.; Cao, J.; Singh, V.; Tiedt, S.; Hundeshagen, G.; Li, T. & Boehme, J. D. et al. (2021)
Immunity, 54(4) pp. 648.e8-659.e8. DOI: https://doi.org/10.1016/j.immuni.2021.02.004
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Details
- Authors
- 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; Liesz, Arthur
- 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-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.
- Issue Date
- 2021
- Journal
- Immunity
- Project
- TRR 274: Checkpoints of Central Nervous System Recovery
TRR 274 | A02: Targeting microglia for the resolution of chronic neuroinflammation after stroke - Working Group
- RG Liesz (Stroke-Immunology)
- ISSN
- 1074-7613
- eISSN
- 1097-4180
- Language
- English