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@ARTICLE{Enderes:154640,
      author       = {Enderes, Jana and Mallesh, Shilpashree and Schneider,
                      Reiner and Hupa, Kristof J and Lysson, Mariola and
                      Schneiker, Bianca and Händler, Kristian and Schlotmann,
                      Balthasar and Günther, Patrick and Schultze, Joachim L and
                      Kalff, Jörg C and Wehner, Sven},
      title        = {{A} {P}opulation of {R}adio-{R}esistant {M}acrophages in
                      the {D}eep {M}yenteric {P}lexus {C}ontributes to
                      {P}ostoperative {I}leus {V}ia {T}oll-{L}ike {R}eceptor 3
                      {S}ignaling.},
      journal      = {Frontiers in immunology},
      volume       = {11},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DZNE-2021-00288},
      pages        = {581111},
      year         = {2021},
      abstract     = {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.},
      keywords     = {Adaptor Proteins, Vesicular Transport: deficiency / Adaptor
                      Proteins, Vesicular Transport: genetics / Adaptor Proteins,
                      Vesicular Transport: immunology / Animals / CX3C Chemokine
                      Receptor 1: genetics / CX3C Chemokine Receptor 1: immunology
                      / Disease Models, Animal / Female / Gene Expression / Ileus:
                      etiology / Ileus: immunology / Ileus: pathology / Immunity,
                      Innate / Macrophages: classification / Macrophages:
                      immunology / Macrophages: radiation effects / Mice / Mice,
                      Inbred C57BL / Mice, Knockout / Mice, Transgenic / Myenteric
                      Plexus: immunology / Postoperative Complications: etiology /
                      Postoperative Complications: immunology / Postoperative
                      Complications: pathology / Radiation Tolerance: immunology /
                      Receptor, Interferon alpha-beta: deficiency / Receptor,
                      Interferon alpha-beta: genetics / Receptor, Interferon
                      alpha-beta: immunology / Signal Transduction: immunology /
                      Toll-Like Receptor 3: deficiency / Toll-Like Receptor 3:
                      genetics / Toll-Like Receptor 3: immunology /
                      Transplantation Chimera: immunology / TLR3 (Other) / TRIF
                      (Other) / innate immune response (Other) / macrophages
                      (Other) / postoperative ileus (Other)},
      cin          = {PRECISE},
      ddc          = {610},
      cid          = {I:(DE-2719)1013031},
      pnm          = {341 - Molecular Signaling (POF3-341) / 352 - Disease
                      Mechanisms (POF4-352) / 354 - Disease Prevention and Healthy
                      Aging (POF4-354)},
      pid          = {G:(DE-HGF)POF3-341 / G:(DE-HGF)POF4-352 /
                      G:(DE-HGF)POF4-354},
      experiment   = {EXP:(DE-2719)PRECISE-20190321},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33519804},
      pmc          = {pmc:PMC7838642},
      doi          = {10.3389/fimmu.2020.581111},
      url          = {https://pub.dzne.de/record/154640},
}