Induction of mucosal immune responses by bacteria and bacterial components

Bacteria have well documented abilities to induce protective as well as pathogenic mucosal immune responses, with the type of response dependent on the genetically programmed balance of pro- and anti-inflammatory cytokines and T-lymphocyte subsets. Inflammatory bowel disease, especially Crohn disease and periodontal disease, appear to be overly aggressive cellular immune responses to some, but not all, normal resident bacteria. Recent evidence suggests that the balance of protective (probiotic) and aggressive commensal luminal bacterial species is an additional determinant of mucosal homeostasis (tolerance) versus pathogenic immune responses (loss of tolerance) and that this balance can be therapeutically manipulated. Mucosal pathogens elicit a characteristic profile of cytokines from epithelial cells, including chemokines that recruit effector cells to the site of invasion to clear the invading organism. The molecular mechanisms of epithelial attachment and invasion of bacterial pathogens (eg, Salmonella, Shigella, pathogenic Escherichia coli, and Yersinia) and the mechanisms of injury induced by Clostridium difficile toxins and Helicobacter pylori are beginning to be understood, as are the innate and cognate host immune responses to these organisms, leading to novel means to effectively block bacterial injury and induce protective immune responses through immunization.