Variants in Autophagy Genes Affect Susceptibility to Both Crohn's Disease and Helicobacter pylori Infection

Abstract

Helicobacter pylori (H pylori) is a Gram-negative, microaerophilic bacterium that selectively colonizes the stomachs of half the world’s human population. H pylori is the etiologic agent of several gastric diseases, including chronic gastritis and peptic ulcers. Long-term, chronic inflammation subsequently increases the risk for the development of mucosa-associated lymphoid tissue lymphoma and gastric cancer.1,2 During a well-choreographed interaction between the bacteria and the host gastric epithelium, H pylori infection initiates an immune response that leads to a massive infiltration of inflammatory cells.1 An evolutionarily conserved cellular mechanism, autophagy, functions as an innate defense lysosomal pathway in response to infection to degrade intracellular micro-organisms attempting to establish a replicative niche in the host epithelial cell cytoplasm.3 Unfortunately, H pylori utilizes a novel escape mechanism to evade lysosomal destruction in host epithelial cells that subsequently supports chronic infection. A study in this month’s issue of Gastroenterology identifies, for the first time, an autophagy gene as a candidate for host susceptibility to H pylori infection and disease progression.4