| First Author | Enderes J | Year | 2020 |
| Journal | Front Immunol | Volume | 11 |
| Pages | 581111 | PubMed ID | 33519804 |
| Mgi Jnum | J:337293 | Mgi Id | MGI:6729397 |
| Doi | 10.3389/fimmu.2020.581111 | Citation | Enderes J, et al. (2020) A Population of Radio-Resistant Macrophages in the Deep Myenteric Plexus Contributes to Postoperative Ileus Via Toll-Like Receptor 3 Signaling. Front Immunol 11:581111 |
| abstractText | 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-beta (TRIF) signaling pathway in POI. POI was induced by small bowel intestinal manipulation in wt, TRIF(-/-), TLR3(-/-), type I interferon receptor(-/-) and interferon-beta 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 MHCII(hi)CX3CR1(-) IBA-1(+) resident macrophage population within the deep myenteric plexus. TLR3 deficiency in these cells, but not in MHCII(hi)CX3CR1(+) 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 MHCII(hi)CX3CR1(-) IBA-1(+) macrophages during POI. Deficiency in TLR3/TRIF protects mice from POI. These data suggest that TLR3 antagonism may prevent POI in humans. |
