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Contact: Dr. Huan-Yao Lei
hylei@mail.ncku.edu.tw
886-623-53535
Society for Experimental Biology and Medicine

Helicobacter pylori can multiply in autophagic vesicles

Helicobacter pylori, a Gram-negative, flagellated, microaerophilic bacterium, can selectively colonize in the human stomach. Its infection is widespread throughout the world, and is present in about 50% of the global human population with 80% in developing countries and 20-50% in industrialized countries. Infection of the stomach with H. pylori induces a local immune response with infiltration of the mucosa by macrophages, neutrophils and lymphocytes. Although the innate and adaptive immune responses are activated, the bacterium is rarely eliminated and infections can last for decades if left untreated. Most infections are asymptomatic, but overt diseases can occur in 10-20 % of infected individuals. The disease spectrum ranges from gastritis to peptic ulceration disease. A long-term chronic infection will increase the risk to gastric adenocarcinoma and mucosa-associated lymphoid-tissue lymphoma. It has been classified as a class I carcinogen by the WHO. Despite intensive studies, and the award of the 2005 Nobel Prize in Physiology for the discovery of the bacterium H. pylori by Robin Warren and Barry Marshall, our understanding of H. pylori-infection-caused disease is still limited. H. pylori has evolved several mechanisms to increase its adherence and persistence in the host. In addition, it must also evade immune clearance. Elimination of H. pylori by phagocytes is inefficient because H. pylori exhibits several virulence factors to evade opsonization, retard phagocytosis, and disrupt membrane trafficking and phagosome maturation after internalization of the microorganism.

In the February 2009 issue of Experimental Biology and Medicine researchers at the National Cheng Kung University, Tainan, Taiwan, have reported a novel phenomenon involving autophagosome formation induced by H. pylori infection and subsequent adoption of these autophagic vesicles by H. pylori for replication in macrophages. The fate of H. pylori is dependent on the strains (isolates) as well as the host macrophages used. Several clinical isolates of H. pylori from Taiwanese patients, but not standard strains, can multiply in the double-layered vesicles of macrophages. The senior author, Dr. Huan-Yao Lei stated that "The autophagy induction by H. pylori is not only found in macrophages, but also in dendritic cells and gastric epithelial cells". This new finding has several implications for the life cycle of H. pylori in the host. H. pylori can be considered as a kind of intracellular microorganism because it can invade host cells to undergo replication within the autophagosome. The bacterium's residence inside infected cells not only increases its resistance to antibiotic treatment, but also avoids neutralization by anti-H. pylori antibodies. In view of the critical role of dendritic cells in presenting H. pylori antigen to initiate the immune response, it is possible that H. pylori-infected dendritic cells induce an inadequate immune response to H. pylori infection that might hinder the clearance of this bacterium. Alternatively, the various immunopathogenesis during the H. pylori-caused diseases might be caused by an unbalanced Th-1 or Th2-mediated response post infection. Finally, the micro-heterogeneity of Taiwanese H. pylori isolates used in this study provides an important hint as to why this microorganism causes so broad a spectrum of diseases. Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine stated "This study also has potential implications for new anti-H. pylori drugs that target the enhancement of autophagy. Dr. Lei and his co-workers have provided an important contribution to our understanding of H. pylori infection."

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Experimental Biology and Medicine is a journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences. The journal was first established in 1903. Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn about the benefits of society membership visit www.sebm.org. If you are interested in publishing in the journal please visit www.ebmonline.org.



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