Figure 3.

Potential mechanisms of the adaptive immune response towards gut microbiota in chronic inflammation. Increased numbers of pathogenic bacteria (e.g. Clostridium difficile, Chlamydia pneumonia, Listeria monocytogenes) have been reported in IBD patients (50). During chronic inflammation, functional cytotoxic CD8⁺ Tc1 cells might be predominantly generated. The disruption of the epithelial barrier might occur by the cytotoxic effect of commensal-specific Tc1 recognizing peptides derived from commensal bacteria on the MHC-I of epithelial cells. Once the epithelial barrier is broken, bacteria can pass freely to the lamina propria initiating an immune response by members of the innate immune system (e.g. macrophages). Due to the plasticity of the cells and a highly pro-inflammatory milieu, CD8⁺ T regs might be driven towards Tc1 or IFN⁺ T regs, making the damage even greater. Trm express pro-inflammatory genes in the context of inflammation. Those pro-inflammatory Trm might be derived from pro-inflammatory Tc1 and Tc17, and some clones might exit the tissue via the blood stream and initiate inflammation in other tissue outside the gastrointestinal tract. DC, dendritic cell; GrB, granzyme B; IFNγ, interferon gamma; IL, interleukin; MHC-I, major histocompatibility complex class I; PP, Peyer´s patch; Tc1 or CTL, cytotoxic T lymphocyte; Tc17, IL17-producing CD8⁺ T cells; TGFβ, transforming growth factor beta; T reg, CD8⁺ T regulatory cell.