| First Author | Roth S | Year | 2021 |
| Journal | Immunity | Volume | 54 |
| Issue | 4 | Pages | 648-659.e8 |
| PubMed ID | 33667383 | Mgi Jnum | J:305309 |
| Mgi Id | MGI:6706436 | Doi | 10.1016/j.immuni.2021.02.004 |
| Citation | Roth S, et al. (2021) Post-injury immunosuppression and secondary infections are caused by an AIM2 inflammasome-driven signaling cascade. Immunity 54(4):648-659.e8 |
| abstractText | 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-1beta (IL-1beta) 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. |
