The Sweeping Role of Cholesterol Depletion in the Persistence of Helicobacter pylori Infections.

The Sweeping Role of Cholesterol Depletion in the Persistence of Helicobacter pylori Infections. Curr Top Microbiol Immunol. 2019;421:209-227 Authors: Morey P, Meyer TF Abstract The ability of Helicobacter pylori to persist lifelong in the human gastric mucosa is a striking phenomenon. It is even more surprising since infection is typically associated with a vivid inflammatory response. Recent studies revealed the mechanism by which this pathogen inhibits the epithelial responses to IFN-γ and other central inflammatory cytokines in order to abolish an effective antimicrobial defense. The mechanism is based on the modification and depletion of cholesterol by the pathogen's cholesterol-α-glucosyltransferase. It abrogates the assembly of numerous cytokine receptors due to the reduction of lipid rafts. Particularly, the receptors for IFN-γ, IL-22, and IL-6 then fail to assemble properly and to activate JAK/STAT signaling. Consequently, cholesterol depletion prevents the release of antimicrobial peptides, including the highly effective β-defensin-3. Intriguingly, the inhibition is spatially restricted to heavily infected cells, while the surrounding epithelium continues to respond normally to cytokine stimulation, thus providing a platform of the intense inflammation typically observed in H. pylori infections. It appears that pathogen and host establish a homeostatic balance between tightly colonized and rather inflamed sites. This ho...
Source: Current Topics in Microbiology and Immunology - Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research