Innate immune defence in the human gastrointestinal tract.

The mucosal surface of the gastrointestinal tract represents a major entry point and ecological niche for many microbes. It forms an important immune barrier, absorbing nutrients, whilst preventing invasion by organisms. Of the extra-ordinarily diverse species that comprise the microbial world, relatively few organisms are able to succeed in breaching this barrier in an otherwise healthy host. The production and secretion of antimicrobial peptides (AMPs) from surface epithelia and circulating immune cells are likely to play a key role in host protection and homeostasis. A number of these peptides are constitutively produced providing resident protection, whereas others are induced during infection and inflammation. In addition to directly eradicating microorganisms, it is becoming increasingly apparent that AMPs are multi-functional with diverse immuno-modulatory properties. This review focuses on three families of AMPs, defensins, cathelicidins, and lysozyme, and discusses their role in mucosal defence.

Differential regulation of beta-defensin gene expression during Cryptosporidium parvum infection.

Invasion of enterocytes by pathogenic microbes evokes both innate and adaptive immune responses, and microbial pathogens have developed strategies to overcome the initial host immune defense. beta-Defensins are potentially important endogenous antibiotic-like effectors of innate immunity expressed by intestinal epithelia. In this study, the interplay between the enteric protozoan parasite Cryptosporidium parvum and host epithelial beta-defensin expression was investigated. Using human and murine models of infection, we demonstrated that C. parvum infection differentially regulates beta-defensin gene expression. Downregulation of murine beta-defensin-1 mRNA and protein was observed in both in vitro and in vivo models of infection. Infection of the human colonic HT29 cell line with the parasite resulted in differential effects on various members of the defensin gene family. Partial reduction in human beta-defensin-1 (hBD-1), induction of hBD-2, and no effect on hBD-3 gene expression was observed. Recombinant hBD-1 and hBD-2 peptides exhibited significant antimicrobial activity against C. parvum sporozoites in vitro. These findings demonstrate that C. parvum infection of enterocytes may affect the expression of various defensins in different ways and suggest that the overall outcome of the effect of antimicrobial peptides on early survival of the parasite may be complex.

Host anti-microbial response to Helicobacter pylori infection.

beta-Defensin peptides are known to be potent anti-bacterials with a wide spectrum of activity. They, therefore, represent an important aspect of innate immunity. In the present study, we have extended our understanding of the regulation of the beta-defensins in response to Helicobacter pylori (H. pylori) infection. We found elevated levels of hBD2 and hBD3 transcripts within gastric cells following infection. This was reflected by increased secretion of the corresponding peptide. The relative bactericidal potency of the beta-defensins was also assessed. Our findings show that hBD3 was the most potent peptide tested followed by hBD2 and hBD1. Relatively modest synergy between hBD1 and hBD2 was also noted. More importantly, we observed endogenous production of putative anti-microbial factors by infected gastric epithelial cells. Our study highlights the active participation of the epithelium in protection against potential pathogens.