Peripheral TREM1 responses to brain and intestinal immunogens amplify stroke severity
| Autor: | Hong Bo Ye, Qian Wang, Paras S. Minhas, Swapnil Mehta, Edward N. Wilson, Mehrdad Shamloo, Xi Yang, Joshua D. Rabinowitz, Jing Wang, Samuel Yang, Stephanie Tran, Rachel K. Lam, Christoph Mueller, Emily M. Johnson, Ling Liu, Michelle L. James, Michelle S. Swarovski, Katrin I. Andreasson, Qingkun Liu |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Neutrophils Immunology Ischemia Spleen Cell Line Proinflammatory cytokine Mice 03 medical and health sciences 0302 clinical medicine Immune system medicine Animals Immunology and Allergy Intestinal Mucosa 610 Medicine & health Stroke Inflammation Mice Knockout Lamina propria Innate immune system biology business.industry Macrophages Brain medicine.disease Immunity Innate Triggering Receptor Expressed on Myeloid Cells-1 Mice Inbred C57BL RAW 264.7 Cells 030104 developmental biology medicine.anatomical_structure Integrin alpha M biology.protein 570 Life sciences business 030215 immunology |
| Zdroj: | Nature Immunology. 20:1023-1034 |
| ISSN: | 1529-2916 1529-2908 |
| DOI: | 10.1038/s41590-019-0421-2 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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