| First Author | Chang Y | Year | 2025 |
| Journal | Cell Mol Immunol | Volume | 22 |
| Issue | 4 | Pages | 437-455 |
| PubMed ID | 39984674 | Mgi Jnum | J:390849 |
| Mgi Id | MGI:8290768 | Doi | 10.1038/s41423-025-01263-0 |
| Citation | Chang Y, et al. (2025) Gut-derived macrophages link intestinal damage to brain injury after cardiac arrest through TREM1 signaling. Cell Mol Immunol 22(4):437-455 |
| abstractText | Brain injury is the leading cause of death and disability in survivors of cardiac arrest, where neuroinflammation triggered by infiltrating macrophages plays a pivotal role. Here, we seek to elucidate the origin of macrophages infiltrating the brain and their mechanism of action after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Wild-type or photoconvertible Cd68-Cre:R26-LSL-KikGR mice were subjected to 10-min CA/CPR, and the migration of gut-derived macrophages into brain was assessed. Transcriptome sequencing was performed to identify the key proinflammatory signal of macrophages infiltrating the brain, triggering receptor expressed on myeloid cells 1 (TREM1). Upon drug intervention, the effects of TREM1 on post-CA/CPR brain injury were further evaluated. 16S rRNA sequencing was used to detect gut dysbiosis after CA/CPR. Through photoconversion experiments, we found that small intestine-derived macrophages infiltrated the brain and played a crucial role in triggering secondary brain injury after CA/CPR. The infiltrating peripheral macrophages showed upregulated TREM1 levels, and we further revealed the crucial role of gut-derived TREM1(+) macrophages in post-CA/CPR brain injury through a drug intervention targeting TREM1. Moreover, a close correlation between upregulated TREM1 expression and poor neurological outcomes was observed in CA survivors. Mechanistically, CA/CPR caused a substantial expansion of Enterobacter at the early stage, which ignited intestinal TREM1 signaling via the activation of Toll-like receptor 4 on macrophages through the release of lipopolysaccharide. Our findings reveal essential crosstalk between the gut and brain after CA/CPR and underscore the potential of targeting TREM1(+) small intestine-derived macrophages as a novel therapeutic strategy for mitigating post-CA/CPR brain injury. |
