A Population of Radio-Resistant Macrophages in the Deep Myenteric Plexus Contributes to Postoperative Ileus Via Toll-Like Receptor 3 Signaling
| Autor: | Jana Enderes, Shilpashree Mallesh, Reiner Schneider, Kristof J. Hupa, Mariola Lysson, Bianca Schneiker, Kristian Händler, Balthasar Schlotmann, Patrick Günther, Joachim L. Schultze, Jörg C. Kalff, Sven Wehner |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Gene Expression immunology [Signal Transduction] genetics [Toll-Like Receptor 3] postoperative ileus immunology [Ileus] Mice 0302 clinical medicine Immunology and Allergy Medicine TLR3 TRIF Mice Knockout Toll-like receptor education.field_of_study pathology [Ileus] etiology [Postoperative Complications] deficiency [Adaptor Proteins Vesicular Transport] immunology [Macrophages] classification [Macrophages] macrophages radiation effects [Macrophages] immunology [Postoperative Complications] 030220 oncology & carcinogenesis Female genetics [Adaptor Proteins Vesicular Transport] immunology [Adaptor Proteins Vesicular Transport] lcsh:Immunologic diseases. Allergy immunology [Transplantation Chimera] immunology [Toll-Like Receptor 3] Immunology Population deficiency [Receptor Interferon alpha-beta] genetics [CX3C Chemokine Receptor 1] Mice Transgenic chemical and pharmacologic phenomena immunology [Receptor Interferon alpha-beta] etiology [Ileus] Proinflammatory cytokine immunology [CX3C Chemokine Receptor 1] 03 medical and health sciences genetics [Receptor Interferon alpha-beta] Animals ddc:610 education Innate immune system business.industry deficiency [Toll-Like Receptor 3] immunology [Myenteric Plexus] Immunity Innate Mice Inbred C57BL Disease Models Animal TLR2 030104 developmental biology innate immune response TLR4 pathology [Postoperative Complications] lcsh:RC581-607 business immunology [Radiation Tolerance] |
| Zdroj: | Frontiers in Immunology, Vol 11 (2021) Frontiers in immunology 11, 581111 (2021). doi:10.3389/fimmu.2020.581111 |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2020.581111 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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