Figure 1.

Mechanisms of intestinal homeostasis. Protection against the enormous load of luminal bacterial content is accomplished through the application of sequential mucosal checkpoints (indicated with the red-cross circles). These checkpoints are organized into three distinct but highly overlapping barriers. The mechanical barrier sustains the physical separation between intraluminal microorganisms and the gut epithelial lining. The antimicrobial barrier consists of nature peptides which act as physical antibiotics against those bacteria that achieve a close contact to the epithelium. Finally, the immunological barrier handles the occasional microbial intruders by efficient intracellular recognition and processing and by regulating the presentation of intraluminal antigens in a manner that leads to the generation of anti-inflammatory/regulatory responses. Both the innate and adaptive arms of immunity are involved in the regulation of this mucosal “immunostat” function. Dashed lines enclose the elements participating in each barrier and demonstrate the overlap between them. APC: antigen-presenting cell.