Wunder C et al. (2006) Cholesterol glucosylation promotes immune evasion by Helicobacter pylori. Nat Med 12: 1030–1038

Helicobacter pylori infection persists in vivo despite the presence of an ongoing host immune response. A new study by Wunder et al. has shown that the balance between persistence of infection and bacterial clearance by the immune response is influenced by H. pylori's glycosylation of cholesterol to cholesteryl α-glucosides—a previously unrecognized mechanism of immune evasion.

The authors showed that H. pylori moves along an increasing cholesterol gradient in vitro, and extracts cholesterol directly from host cell membranes. H. pylori cholesterol α-glucosyltransferase, a newly identified enzyme, converts cholesterol into cholesteryl α-glucosides—these products were found to be essential to H. pylori's evasion of phagocytosis, T-cell activation and bacterial clearance in vivo. The authors also demonstrated that the balance between cholesterol and cholesteryl α-glucosides determines whether bacterial clearance or immune evasion occurs: the presence of excess cholesterol in the stomach resulted in reduced H. pylori burden and increased gastric inflammation, mediated by an increase in phagocytosis of H. pylori by antigen-presenting cells and induction of vigorous, antigen-specific, T-cell activation. Intriguingly, H. pylori seems to undergo only limited phagocytosis; Wunder et al. speculate that release of cholesteryl α-glucosides within antigen-presenting cells could reduce subsequent phagocytosis of H. pylori, or might influence downstream signaling via membrane receptors.

Wunder et al. suggest that treatments could be developed that inhibit cholesterol glucosylation and thereby render H. pylori accessible to the immune system. Such novel treatments are desperately needed, given the poor compliance and suboptimal eradication rates associated with conventional triple therapy regimens.