Analysis of the Relative Contribution of Phagocytosis, LC3‐Associated Phagocytosis, and Canonical Autophagy During Helicobacter pylori Infection of Macrophages. Issue 6 (10th April 2015)

• Record Type: Journal Article
• Authors: Deen, Nadia S.; Gong, Lan; Naderer, Thomas; Devenish, Rodney J.; Kwok, Terry
• Is Part Of: Helicobacter. Volume 20:Issue 6(2015:Dec.)
• Page Start: 449
• Page End: 459
• Publication Date: 2015-04-10
• Subjects: Helicobacter pylori -- autophagy -- autophagosomes -- LC3‐associated phagocytosis (LAP) -- phagocytosis -- macrophages; Helicobacter -- Periodicals; Helicobacter infections -- Periodicals; Stomach -- Diseases -- Periodicals; 616.3301405
• DOI: 10.1111/hel.12223
• Languages: English
• ISSNs: 1083-4389

Abstract

Abstract: Background: Previous findings have suggested that Helicobacter pylori induces autophagic processes and subsequently takes refuge in autophagosomes, thereby contributing to persistent infection. Recently, a noncanonical form of autophagy, LC3 (microtubule‐associated protein 1 light chain 3)‐associated phagocytosis (LAP), has been shown to be required for efficient clearance of some intracellular bacteria. Whether H. pylori infection induces LAP had not been examined previously. In this study, we determined the extent to which H. pylori infection induces canonical autophagy or LAP in macrophages, and the involvement of the H. pylori cag pathogenicity island ( cag PAI) with these processes. Methods: Immunofluorescence confocal microscopy was used to analyze the formation of GFP‐LC3 puncta and their colocalization with H. pylori . Transmission electron microscopy was used to detect the ultrastructure of H. pylori ‐containing compartments. Results: The majority of intracellular bacteria (85–95%) were found in phagosomes that were LC3‐negative, with a small proportion (4–14%) appearing "free" in the cytosol. Only a very small percentage (0.5–6%) of intracellular H. pylori was sequestered in autophagosomes. Furthermore, no statistically significant difference in the relative distribution of H. pylori in the various compartments was observed between wild‐type and cag PAI‐mutant bacteria. Conclusions: In macrophages, H. pylori infection does not induce LAP, but can induce canonical autophagy, which entraps a very small fraction of intracellular bacteria. We propose that this subpopulation of intracellular H. pylori might have escaped from phagosomes into the cytosol before being sequestered by autophagosomes. The cag PAI of H. pylori has only minor influence, if any, on the extent of these processes.