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| Home > Publications Database > A Population of Radio-Resistant Macrophages in the Deep Myenteric Plexus Contributes to Postoperative Ileus Via Toll-Like Receptor 3 Signaling. |
| Home > Publications Database > A Population of Radio-Resistant Macrophages in the Deep Myenteric Plexus Contributes to Postoperative Ileus Via Toll-Like Receptor 3 Signaling. |
| Journal Article | DZNE-2021-00288 |
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2021
Frontiers Media
Lausanne
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Please use a persistent id in citations: doi:10.3389/fimmu.2020.581111
Abstract: Postoperative ileus (POI) is triggered by an innate immune response in the muscularis externa (ME) and is accompanied by bacterial translocation. Bacteria can trigger an innate immune response via toll-like receptor (TLR) activation, but the latter's contribution to POI has been disproved for several TLRs, including TLR2 and TLR4. Herein we investigated the role of double-stranded RNA detection via TLR3 and TIR-domain-containing adapter-inducing interferon-β (TRIF) signaling pathway in POI. POI was induced by small bowel intestinal manipulation in wt, TRIF-/-, TLR3-/-, type I interferon receptor-/- and interferon-β reporter mice, all on C57BL/6 background, and POI severity was quantified by gene expression analysis, gastrointestinal transit and leukocyte extravasation into the ME. TRIF/TLR3 deficiency reduced postoperative ME inflammation and prevented POI. With bone marrow transplantation, RNA-sequencing, flow cytometry and immunohistochemistry we revealed a distinct TLR3-expressing radio-resistant MHCIIhiCX3CR1- IBA-1+ resident macrophage population within the deep myenteric plexus. TLR3 deficiency in these cells, but not in MHCIIhiCX3CR1+ macrophages, reduced cytokine expression in POI. While this might not be an exclusive macrophage-privileged pathway, the TLR3/TRIF axis contributes to proinflammatory cytokine production in MHCIIhiCX3CR1- IBA-1+ macrophages during POI. Deficiency in TLR3/TRIF protects mice from POI. These data suggest that TLR3 antagonism may prevent POI in humans.
Keyword(s): Adaptor Proteins, Vesicular Transport: deficiency (MeSH) ; Adaptor Proteins, Vesicular Transport: genetics (MeSH) ; Adaptor Proteins, Vesicular Transport: immunology (MeSH) ; Animals (MeSH) ; CX3C Chemokine Receptor 1: genetics (MeSH) ; CX3C Chemokine Receptor 1: immunology (MeSH) ; Disease Models, Animal (MeSH) ; Female (MeSH) ; Gene Expression (MeSH) ; Ileus: etiology (MeSH) ; Ileus: immunology (MeSH) ; Ileus: pathology (MeSH) ; Immunity, Innate (MeSH) ; Macrophages: classification (MeSH) ; Macrophages: immunology (MeSH) ; Macrophages: radiation effects (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Knockout (MeSH) ; Mice, Transgenic (MeSH) ; Myenteric Plexus: immunology (MeSH) ; Postoperative Complications: etiology (MeSH) ; Postoperative Complications: immunology (MeSH) ; Postoperative Complications: pathology (MeSH) ; Radiation Tolerance: immunology (MeSH) ; Receptor, Interferon alpha-beta: deficiency (MeSH) ; Receptor, Interferon alpha-beta: genetics (MeSH) ; Receptor, Interferon alpha-beta: immunology (MeSH) ; Signal Transduction: immunology (MeSH) ; Toll-Like Receptor 3: deficiency (MeSH) ; Toll-Like Receptor 3: genetics (MeSH) ; Toll-Like Receptor 3: immunology (MeSH) ; Transplantation Chimera: immunology (MeSH) ; TLR3 ; TRIF ; innate immune response ; macrophages ; postoperative ileus
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