Bacterial mucosa cross-talk and pathophysiology of inflammation

The intestinal mucosa harbors a complexly organized immune system, which accomplishes important, partially contradictory surveillance and protective functions. It has to protect the host from potential external (microbial and nonmicrobial) aggression, whereas at the same time avoiding an inflammatory reaction toward harmless antigenic structures of microbial (commensal microflora) or alimentary origin. Professional sentinels (of the innate immune system) are in close and interactive contact with the intestinal microflora, which plays via this exchange an important role during the postnatal period in the maturation of the intestinal immune system. The innate immune system is a key regulator of local and systemic immune responses, including the adaptive immune system. Distinct signals induce tolerance to specific antigens presented by intestinal dendritic cells, whereas proinflammatory mediators easily switch these tolerogenic responses toward protective or destructive inflammatory reactions. Given the intense exchange between the intestinal microflora and the mucosal immune system, a permanent but actively controlled and downregulated physiological inflammation characterizes the intestinal mucosa. Therefore, it is easily conceivable that perturbation of the intestinal microflora or immune control mechanisms can initiate or contribute to pathological and potentially chronic inflammatory reactions, such as seen in inflammatory bowel diseases.