Journal
NATURE IMMUNOLOGY
Volume 20, Issue 8, Pages 1023-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41590-019-0421-2
Keywords
-
Categories
Funding
- National Institutes of Health (NIH) grant [R01NS045727, R21NS087639, R01NS100180, RO1AG053001]
- Paul and Daisy Soros Fellowship for New Americans
- Gerald J. Lieberman Fellowship
- Stanford Medicine Dean's Fellowship
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available