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Post-injury immunosuppression and secondary infections are caused by an AIM2 inflammasome-driven signaling cascade.
- Source :
-
Immunity [Immunity] 2021 Apr 13; Vol. 54 (4), pp. 648-659.e8. Date of Electronic Publication: 2021 Mar 04. - Publication Year :
- 2021
-
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.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Apoptosis immunology
Bacterial Infections immunology
Burns immunology
Burns microbiology
Coinfection microbiology
Humans
Interleukin-1beta immunology
Mice
Mice, Inbred C57BL
Monocytes immunology
Stroke immunology
Stroke microbiology
T-Lymphocytes immunology
Coinfection immunology
DNA-Binding Proteins immunology
Immune Tolerance immunology
Inflammasomes immunology
Signal Transduction immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4180
- Volume :
- 54
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Immunity
- Publication Type :
- Academic Journal
- Accession number :
- 33667383
- Full Text :
- https://doi.org/10.1016/j.immuni.2021.02.004