当前位置:首页 / 科学研究 / 实验室 / 正文

实验室

10:00-11:00, Tuesday, December 11, 2018


Speaker: Thomas F. Meyer Ph.D.

Director

Max Planck Institute for Infection Biology

Berlin, Germany

Topic: Helicobacter pylori-driven inflammation and immune evasion – a fatal pair paving the way for carcinogenesis

Host: Feng Shao, Ph.D.

Abstract

Helicobacter pylori, one of the most successful pathogens, which colonizes the stomachs of about 50% of the world’s population, is implicated in various gastric diseases, including carcinogenesis. We have recently identified a key inflammatory factor of H. pylori, released via the pathogen’s type 4 secretion system. It is an ADP-heptose that functions as an intermediate of LPS synthesis and is recognized in the mucosal epithelium by the novel pattern recognition kinase Alpk1. Subsequent phosphorylation of TIFA then leads to the activation of NF-κB and the release of pro-inflammatory chemokines. The ensuing recruitment of immune cells to the infected sites, where they mount a vivid inflammatory response, dampens the infection somewhat, but is unable to eliminate the pathogen. Our recent work identified the mechanism underlying this crucial failure, which is due to the pathogen’s cholesterol-α-glucosyl transferase (CGT). It facilitates the extraction of host cell cholesterol from the epithelial membranes, effectively degrading lipid rafts, thereby rendering host cells unable to respond to a number of inflammatory cytokines, such as IFNγ and IL22. The resulting failure of JAK/STAT activation and downstream transcriptional signaling prevents the release of antimicrobial peptides, including the highly effective β-defensin 3 (hBD3). These conditions facilitate the chronic colonization with H. pylori in the gastric mucosa and may nurture the emergence of mutant cells as the starting point of malignant transformation. Our observations further explain ongoing failures in the development of a vaccine against this carcinogenic bacterium. Nonetheless, we expect our insights will lead to a better understanding of the mechanism of gastric pathogenesis as a basis for novel preventive measures.