| First Author | Liu Q | Year | 2019 |
| Journal | Nat Immunol | Volume | 20 |
| Issue | 8 | Pages | 1023-1034 |
| PubMed ID | 31263278 | Mgi Jnum | J:289316 |
| Mgi Id | MGI:6434988 | Doi | 10.1038/s41590-019-0421-2 |
| Citation | Liu Q, et al. (2019) Peripheral TREM1 responses to brain and intestinal immunogens amplify stroke severity. Nat Immunol 20(8):1023-1034 |
| abstractText | Stroke is a multiphasic process in which initial cerebral ischemia is followed by secondary injury from immune responses to ischemic brain components. Here we demonstrate that peripheral CD11b(+)CD45(+) myeloid cells magnify stroke injury via activation of triggering receptor expressed on myeloid cells 1 (TREM1), an amplifier of proinflammatory innate immune responses. TREM1 was induced within hours after stroke peripherally in CD11b(+)CD45(+) cells trafficking to ischemic brain. TREM1 inhibition genetically or pharmacologically improved outcome via protective antioxidant and anti-inflammatory mechanisms. Positron electron tomography imaging using radiolabeled antibody recognizing TREM1 revealed elevated TREM1 expression in spleen and, unexpectedly, in intestine. In the lamina propria, noradrenergic-dependent increases in gut permeability induced TREM1 on inflammatory Ly6C(+)MHCII(+) macrophages, further increasing epithelial permeability and facilitating bacterial translocation across the gut barrier. Thus, following stroke, peripheral TREM1 induction amplifies proinflammatory responses to both brain-derived and intestinal-derived immunogenic components. Critically, targeting this specific innate immune pathway reduces cerebral injury. |
