Epithelial cell-specific MyD88 signaling mediates ischemia/reperfusion-induced intestinal injury independent of microbial status.

摘要: The intestinal epithelium constitutes a crucial physical barrier separating the host from luminal compartment containing various noxious agents such as bacteria, bacterial products, and food-derived particles.1–3 In addition to its function, responds numerous stimuli through action of conserved innate sensors Toll-like receptors (TLRs).4 case commensal this dialogue between microbiota epithelial cells (IECs) is important for maintenance homeostasis induction antimicrobial peptides, toning adaptive immune responses, fortification barrier.5 A compromised could have deleterious consequences contents may gain access mucosal system enter systemic circulation, triggering damaging cell response. constantly facing injury caused by irritants, but these episodes rarely lead life-threatening situations because has developed an efficient wound-healing response maintain homeostasis.6 However, extreme challenges hypoxic, ischemic, or radiation events often overpower response, thereby exposing products. For example, ischemia can sepsis translocation.7 Intestinal ischemia–reperfusion (I/R) occur under several clinical conditions like sepsis, hemorrhage, mesenteric due blood clots, neonatal necrotizing enterocolitis, even small bowel transplantation.8 Reperfusion after ischemic causes death disruption function leading invasion bacteria.9 Antibiotic use mainstay treatment prevent translocation been shown be protective before inciting event.10 Interestingly, seems play role in experimental models including dextran sodium sulfate radiation.11–13 contrast, global deletion myeloid differentiation primary gene (Myd88), adaptor protein signaling, protects mice I/R-induced injury.14 Moreover, model enterocolitis newborn mice, TLR/MyD88-mediated controlled nucleotide-binding oligomerization domain-2 signaling.15 microbes I/R still unclear most studies linking bacteria used reduction strategies (antibiotic treatment) and/or sensor-deficient mice. Numerous cells, IEC express MyD88, type specific molecule I/R-mediated unknown. In study, we investigated impact using germ-free conventionalized defined IEC-specific MyD88 signaling injury. We report that IEC-derived promotes This effect likely mediated 2 main events: (1) IEC-dependent increased amount IgA subsequent complement activation during phase (2) IEC-MyD88–dependent expression neutrophil chemoattractants IECs, further tissue.