Are not so clear-cut. The truth is, these cells could aid in restitution with the epithelial barrier in IBD individuals. As notedFrontiers in Immunology www.frontiersin.orgThe intestinal epithelium is uniquely located to be the perfect initial line of defense or communication with intraluminal bacteria and viruses. A number of bacteria alter cytokine production by the gut epithelium (Figure 5) (9803). Exposure on the colon epithelial cell line HCT-8 to Shiga toxin 2 produced by Shigatoxigenic Escherichia coli enhanced protein expression of IL-8 and TNF-. Having said that, HCT-8 exposure to subtilase cytoxin made by precisely the same bacterium decreased protein expression of IL-8 and monocyte chemoattractant Mineralocorticoid Receptor Formulation protein-1 relative to unstimulated handle cells, suggesting that these bacteria could use precise toxin production to differentially modulate host defenses (98). Infection of Caco-2 monolayers with Shigella flexneri 2a or Shigella dysente riae 1 induced IL-8 secretion, which was predominantly released from the basolateral aspect of your epithelial cells, and Salmonella enterica serovar Typhimurium activated non-canonical inflammasome activity in murine and human intestinal epithelial cells, facilitating IL-18 secretion and bacterial clearance (99, 100). In contrast to these predominantly pro-inflammatory responses, stimulation of Caco-2 cells with commensal bacteria elevated thymic HCV Protease Inhibitor Gene ID stromal lymphopoietin (TSLP), IL-8, and TGF-1 secretion, which resulted in the promotion of a tolerogenic dendritic cell phenotype by TSLP and TGF-1 (101). In addition, probiotic bacterial strains have been shown to minimize gut epithelial production of IL-8 (102, 103). Intestinal epithelial cytokine release prompted by viral infection might help clear infection or make pathology. Simian immunodeficiency virus infection on the intestinal epithelium of rhesus macaques induced IL-1 expression by Paneth cells just before the induction of an antiviral IFN response. IL-1 expression was correlated with epithelial disruption characterized by the mislocalization and lowered expression of tight junction proteins, despite the fact that these alterations did not correspond to any aberrant responses to bacteria (104). Numerous research have documented the production of IFN- by virus-infected intestinal epithelial cells, despite the fact that the potential of this cytokine to limit viral infection varied in between studies (82, 84, 105). A attainable explanation for these discrepancies may very well be identified within the work of Hern dez et al., which demonstrated that group 3 ILC-derived IL-22 amplified IFN- signaling in intestinal epithelial cells, and synergistic signaling by the two cytokines was vital to get a reduction in viral replication and optimal stimulation of IFN-induced gene expression (105).June 2018 Volume 9 Articleintestinal epithelial Responses to Pathogens and CommensalsAndrews et al.Cytokine Tuning of Intestinal Epithelial FunctionFiGURe 5 Pathogens, commensal bacteria, and probiotics can boost or diminish the production of cytokines and chemokines by the intestinal epithelium. These interactions could market or deter immune cell infiltration from the gut, such as by growing or minimizing the production of chemokines, such as interleukin (IL)-8 and monocyte chemoattractant protein-1 (MCP-1). In some cases, bacterial interactions using the gut epithelium could instruct the intestinal immune program. For instance, intestinal epithelial cells make thymic stromal lymphopoietin (TSLP) and transforming growth factor- (TGF-) 1 in resp.