Peripheral TREM1 responses to brain and intestinal immunogens amplify stroke severity.

TitlePeripheral TREM1 responses to brain and intestinal immunogens amplify stroke severity.
Publication TypeJournal Article
Year of Publication2019
AuthorsLiu, Q, Johnson, EM, Lam, RK, Wang, Q, Ye, HBo, Wilson, EN, Minhas, PS, Liu, L, Swarovski, MS, Tran, S, Wang, J, Mehta, SS, Yang, X, Rabinowitz, JD, Yang, SS, Shamloo, M, Mueller, C, James, ML, Andreasson, KI
JournalNat Immunol
Date Published2019 Jul 01
ISSN1529-2916
Abstract

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

DOI10.1038/s41590-019-0421-2
Alternate JournalNat. Immunol.
PubMed ID31263278