Regulation of host responses by a bacterial peptide

Helicobacter pylori, like many other pathogenic bacteria, secrete antibiotic substances that give it a competitive advantage over other species for growth in its host's tissues. One such antibiotic is a peptide termed HP (2-20), a relative of the antibacterial protein cecropin, which is expressed by eukaryotes as diverse as flies and mammals. Betten and colleagues now show that HP (2-20), a cleaved fragment of an H. pylori ribosomal protein, also acts directly on the host immune system, apparently allowing the bacterium to alter the course and outcome of an infection. This peptide stimulates monocytes via at least 2 related receptors, FPRL1 and 2. Activated monocytes respond with a burst of reactive oxygen species, which are not only toxic to bacteria, but also potentially carcinogenic to the host. Subsequent changes in NK cell function may also favor the formation of gastric tumors in H. pylori carriers, since exposure of these cells to oxygen radicals alters their pattern of gene expression and impairs their ability to activate antitumor immune responses. Interestingly, the high endogenous levels of histamine in the gastric mucosa appear to block the accumulation of these harmful metabolites, suggesting that histamine helps prevent gastric tumorigenesis in infected individuals.

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