%0 Journal Article
%T Helicobacter pylori phagosome maturation in primary human macrophages
%A Glenn N Borlace
%A Hilary F Jones
%A Stacey J Keep
%A Ross N Butler
%A Doug A Brooks
%J Gut Pathogens
%D 2011
%I BioMed Central
%R 10.1186/1757-4749-3-3
%X All of the H. pylori strains examined showed some disruption to the phagosome maturation process, when compared to control E. coli. The early endosome marker EEA1 and late endosome marker Rab7 were retained on H. pylori phagosomes, while the late endosome-lysosome markers CD63, LAMP-1 and LAMP-2 were acquired in an apparently normal manner. Acquisition of EEA1 by H. pylori phagosomes appeared to occur by two distinct, strain specific modes. H. pylori strains that were negative for the cancer associated virulence factor CagA were detected in phagosomes that recruited large amounts of EEA1 relative to Rab5, compared to CagA positive strains. There were also strain specific differences in the timing of Rab7 acquisition which correlated with differences in the rate of intracellular trafficking of phagosomes and the timing of megasome formation. Megasomes were observed for all of the H. pylori strains examined.H. pylori appeared to disrupt the normal process of phagosome maturation in primary human macrophages, appearing to block endosome fission. This resulted in the formation of a hybrid phagosome-endosome-lysosome compartment, which we propose has reduced degradative capacity. Reduced killing by phagocytes is consistent with the persistence of H. pylori in the host, and would contribute to the chronic stimulation of the inflammatory immune response, which underlies H. pylori-associated disease.Helicobacter pylori (H. pylori) is one of the most successful human pathogens, estimated to have infected half of the world's population [1]. H. pylori colonises the human stomach, is the primary cause of gastric and duodenal ulcers [2], and is a major risk factor for the development of gastric cancer [3,4]. H. pylori strains have been traditionally classified into two types on the basis of virulence factors [5]. Virulent type 1 strains secrete an active form of the vacuolating cytotoxin VacA (s1/m1) and possess the pathogenicity island cagPAI, whereas avirulent type 2 strains s
%U http://www.gutpathogens.com/content/3/1/3