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000154640 0247_ $$2doi$$a10.3389/fimmu.2020.581111
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000154640 037__ $$aDZNE-2021-00288
000154640 041__ $$aEnglish
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000154640 1001_ $$aEnderes, Jana$$b0
000154640 245__ $$aA Population of Radio-Resistant Macrophages in the Deep Myenteric Plexus Contributes to Postoperative Ileus Via Toll-Like Receptor 3 Signaling.
000154640 260__ $$aLausanne$$bFrontiers Media$$c2021
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000154640 520__ $$aPostoperative ileus (POI) is triggered by an innate immune response in the muscularis externa (ME) and is accompanied by bacterial translocation. Bacteria can trigger an innate immune response via toll-like receptor (TLR) activation, but the latter's contribution to POI has been disproved for several TLRs, including TLR2 and TLR4. Herein we investigated the role of double-stranded RNA detection via TLR3 and TIR-domain-containing adapter-inducing interferon-β (TRIF) signaling pathway in POI. POI was induced by small bowel intestinal manipulation in wt, TRIF-/-, TLR3-/-, type I interferon receptor-/- and interferon-β reporter mice, all on C57BL/6 background, and POI severity was quantified by gene expression analysis, gastrointestinal transit and leukocyte extravasation into the ME. TRIF/TLR3 deficiency reduced postoperative ME inflammation and prevented POI. With bone marrow transplantation, RNA-sequencing, flow cytometry and immunohistochemistry we revealed a distinct TLR3-expressing radio-resistant MHCIIhiCX3CR1- IBA-1+ resident macrophage population within the deep myenteric plexus. TLR3 deficiency in these cells, but not in MHCIIhiCX3CR1+ macrophages, reduced cytokine expression in POI. While this might not be an exclusive macrophage-privileged pathway, the TLR3/TRIF axis contributes to proinflammatory cytokine production in MHCIIhiCX3CR1- IBA-1+ macrophages during POI. Deficiency in TLR3/TRIF protects mice from POI. These data suggest that TLR3 antagonism may prevent POI in humans.
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000154640 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x1
000154640 536__ $$0G:(DE-HGF)POF4-354$$a354 - Disease Prevention and Healthy Aging (POF4-354)$$cPOF4-354$$fPOF IV$$x2
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000154640 650_7 $$2Other$$aTLR3
000154640 650_7 $$2Other$$aTRIF
000154640 650_7 $$2Other$$ainnate immune response
000154640 650_7 $$2Other$$amacrophages
000154640 650_7 $$2Other$$apostoperative ileus
000154640 650_2 $$2MeSH$$aAdaptor Proteins, Vesicular Transport: deficiency
000154640 650_2 $$2MeSH$$aAdaptor Proteins, Vesicular Transport: genetics
000154640 650_2 $$2MeSH$$aAdaptor Proteins, Vesicular Transport: immunology
000154640 650_2 $$2MeSH$$aAnimals
000154640 650_2 $$2MeSH$$aCX3C Chemokine Receptor 1: genetics
000154640 650_2 $$2MeSH$$aCX3C Chemokine Receptor 1: immunology
000154640 650_2 $$2MeSH$$aDisease Models, Animal
000154640 650_2 $$2MeSH$$aFemale
000154640 650_2 $$2MeSH$$aGene Expression
000154640 650_2 $$2MeSH$$aIleus: etiology
000154640 650_2 $$2MeSH$$aIleus: immunology
000154640 650_2 $$2MeSH$$aIleus: pathology
000154640 650_2 $$2MeSH$$aImmunity, Innate
000154640 650_2 $$2MeSH$$aMacrophages: classification
000154640 650_2 $$2MeSH$$aMacrophages: immunology
000154640 650_2 $$2MeSH$$aMacrophages: radiation effects
000154640 650_2 $$2MeSH$$aMice
000154640 650_2 $$2MeSH$$aMice, Inbred C57BL
000154640 650_2 $$2MeSH$$aMice, Knockout
000154640 650_2 $$2MeSH$$aMice, Transgenic
000154640 650_2 $$2MeSH$$aMyenteric Plexus: immunology
000154640 650_2 $$2MeSH$$aPostoperative Complications: etiology
000154640 650_2 $$2MeSH$$aPostoperative Complications: immunology
000154640 650_2 $$2MeSH$$aPostoperative Complications: pathology
000154640 650_2 $$2MeSH$$aRadiation Tolerance: immunology
000154640 650_2 $$2MeSH$$aReceptor, Interferon alpha-beta: deficiency
000154640 650_2 $$2MeSH$$aReceptor, Interferon alpha-beta: genetics
000154640 650_2 $$2MeSH$$aReceptor, Interferon alpha-beta: immunology
000154640 650_2 $$2MeSH$$aSignal Transduction: immunology
000154640 650_2 $$2MeSH$$aToll-Like Receptor 3: deficiency
000154640 650_2 $$2MeSH$$aToll-Like Receptor 3: genetics
000154640 650_2 $$2MeSH$$aToll-Like Receptor 3: immunology
000154640 650_2 $$2MeSH$$aTransplantation Chimera: immunology
000154640 693__ $$0EXP:(DE-2719)PRECISE-20190321$$5EXP:(DE-2719)PRECISE-20190321$$ePlatform for Single Cell Genomics and Epigenomics at DZNE  University of Bonn$$x0
000154640 7001_ $$aMallesh, Shilpashree$$b1
000154640 7001_ $$0P:(DE-2719)9001240$$aSchneider, Reiner$$b2$$udzne
000154640 7001_ $$aHupa, Kristof J$$b3
000154640 7001_ $$aLysson, Mariola$$b4
000154640 7001_ $$aSchneiker, Bianca$$b5
000154640 7001_ $$0P:(DE-2719)2812735$$aHändler, Kristian$$b6
000154640 7001_ $$aSchlotmann, Balthasar$$b7
000154640 7001_ $$0P:(DE-2719)2810647$$aGünther, Patrick$$b8
000154640 7001_ $$0P:(DE-2719)2811660$$aSchultze, Joachim L$$b9
000154640 7001_ $$aKalff, Jörg C$$b10
000154640 7001_ $$0P:(DE-HGF)0$$aWehner, Sven$$b11$$eCorresponding author
000154640 773__ $$0PERI:(DE-600)2606827-8$$a10.3389/fimmu.2020.581111$$gVol. 11, p. 581111$$p581111$$tFrontiers in immunology$$v11$$x1664-3224$$y2021
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