A TNF-IL-1 circuit controls Yersinia within intestinal granulomas
Tumor necrosis factor (TNF) is a pleiotropic inflammatory cytokine that mediates antimicrobial defense and granuloma formation in response to infection by numerous pathogens. colonizes the intestinal mucosa and induces recruitment of neutrophils and inflammatory monocytes into organized immune struc...
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Published in | bioRxiv : the preprint server for biology |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
22.04.2023
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Online Access | Get more information |
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Summary: | Tumor necrosis factor (TNF) is a pleiotropic inflammatory cytokine that mediates antimicrobial defense and granuloma formation in response to infection by numerous pathogens.
colonizes the intestinal mucosa and induces recruitment of neutrophils and inflammatory monocytes into organized immune structures termed pyogranulomas that control the bacterial infection. Inflammatory monocytes are essential for control and clearance of
within intestinal pyogranulomas, but how monocytes mediate
restriction is poorly understood. Here, we demonstrate that TNF signaling in monocytes is required for bacterial containment following enteric
infection. We further show that monocyte-intrinsic TNFR1 signaling drives production of monocyte-derived interleukin-1 (IL-1), which signals through IL-1 receptor on non-hematopoietic cells to enable pyogranuloma-mediated control of
infection. Altogether, our work reveals a monocyte-intrinsic TNF-IL-1 collaborative circuit as a crucial driver of intestinal granuloma function, and defines the cellular target of TNF signaling that restricts intestinal
infection. |
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