Home > Publications Database > A Population of Radio-Resistant Macrophages in the Deep Myenteric Plexus Contributes to Postoperative Ileus Via Toll-Like Receptor 3 Signaling. > print

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005     20240925164129.0
024 7 _ |a 10.3389/fimmu.2020.581111
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037 _ _ |a DZNE-2021-00288
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Enderes, Jana
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245 _ _ |a A Population of Radio-Resistant Macrophages in the Deep Myenteric Plexus Contributes to Postoperative Ileus Via Toll-Like Receptor 3 Signaling.
260 _ _ |a Lausanne
|c 2021
|b Frontiers Media
336 7 _ |a article
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520 _ _ |a 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.
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650 _ 7 |a TLR3
|2 Other
650 _ 7 |a TRIF
|2 Other
650 _ 7 |a innate immune response
|2 Other
650 _ 7 |a macrophages
|2 Other
650 _ 7 |a postoperative ileus
|2 Other
650 _ 2 |a Adaptor Proteins, Vesicular Transport: deficiency
|2 MeSH
650 _ 2 |a Adaptor Proteins, Vesicular Transport: genetics
|2 MeSH
650 _ 2 |a Adaptor Proteins, Vesicular Transport: immunology
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a CX3C Chemokine Receptor 1: genetics
|2 MeSH
650 _ 2 |a CX3C Chemokine Receptor 1: immunology
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Gene Expression
|2 MeSH
650 _ 2 |a Ileus: etiology
|2 MeSH
650 _ 2 |a Ileus: immunology
|2 MeSH
650 _ 2 |a Ileus: pathology
|2 MeSH
650 _ 2 |a Immunity, Innate
|2 MeSH
650 _ 2 |a Macrophages: classification
|2 MeSH
650 _ 2 |a Macrophages: immunology
|2 MeSH
650 _ 2 |a Macrophages: radiation effects
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Mice, Knockout
|2 MeSH
650 _ 2 |a Mice, Transgenic
|2 MeSH
650 _ 2 |a Myenteric Plexus: immunology
|2 MeSH
650 _ 2 |a Postoperative Complications: etiology
|2 MeSH
650 _ 2 |a Postoperative Complications: immunology
|2 MeSH
650 _ 2 |a Postoperative Complications: pathology
|2 MeSH
650 _ 2 |a Radiation Tolerance: immunology
|2 MeSH
650 _ 2 |a Receptor, Interferon alpha-beta: deficiency
|2 MeSH
650 _ 2 |a Receptor, Interferon alpha-beta: genetics
|2 MeSH
650 _ 2 |a Receptor, Interferon alpha-beta: immunology
|2 MeSH
650 _ 2 |a Signal Transduction: immunology
|2 MeSH
650 _ 2 |a Toll-Like Receptor 3: deficiency
|2 MeSH
650 _ 2 |a Toll-Like Receptor 3: genetics
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650 _ 2 |a Toll-Like Receptor 3: immunology
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650 _ 2 |a Transplantation Chimera: immunology
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700 1 _ |a Schultze, Joachim L
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700 1 _ |a Kalff, Jörg C
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700 1 _ |a Wehner, Sven
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773 _ _ |a 10.3389/fimmu.2020.581111
|g Vol. 11, p. 581111
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