Figure 2.
Host protection and pathology from pathobiont assault. The induction of protective and pathogenic immune response during infections by pathobionts such as C. difficile and H. hepaticus. During pathogenesis both pathobionts produce toxins such as CDT and TcdA/B causing a disintegration of the epithelial barrier. Leaky gut induces an acute inflammatory response mediated by inflammasome activation leading to induction of IL-1β and IL-23 cytokines. The cytokines activate the proliferation and induction of Th17 response leading to neutrophilia and enhanced inflammatory conditions of pseudomembranous colitis and colitis. On the contrary, pathobiont tolerance can be induced by T cell-dependent group of IgA and IgG antibodies against toxins and production of cytokines such as IFN-γ by ILC1s, IL-22 by ILC3s, promoting complement-mediated phagocytosis of pathobiont. In the case of H. hepaticus, the expression of c-MAF transcription factor induces the production of pathobiont-specific RORγt+FOXP3+ regulatory T(iTreg) cells that confine pro-inflammatory T helper 17 (TH17) cells leading to the tolerance against the pathobiont. IL-33 activates ILC2 that inhibit the proliferation of C. difficile. Microbiota-derived acetate interacts with the FFAR2 receptors on ILC3s and neutrophils, leading to their recruitment to the site of infection and activation of inflammasome and secretion of IL-1β. In response to IL-1β, ILC3 further secretes IL-22 through IL-1 receptor signaling. Illustrations were made using Biorender tool