A Population of Radio-Resistant Macrophages in the Deep Myenteric Plexus Contributes to Postoperative Ileus
| 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 |
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| Rok vydání: | 2020 |
| Předmět: |
Immunology
CX3C Chemokine Receptor 1 Gene Expression Myenteric Plexus chemical and pharmacologic phenomena Mice Transgenic Receptor Interferon alpha-beta Radiation Tolerance postoperative ileus Mice Ileus Postoperative Complications Animals TLR3 TRIF Original Research Mice Knockout Transplantation Chimera Macrophages Immunity Innate Toll-Like Receptor 3 Mice Inbred C57BL Adaptor Proteins Vesicular Transport Disease Models Animal innate immune response Female Signal Transduction |
| Zdroj: | Frontiers in Immunology |
| ISSN: | 1664-3224 |
| 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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