Document Detail


Helicobacter pylori-induced homotypic phagosome fusion in human monocytes is independent of the bacterial vacA and cag status.
MedLine Citation:
PMID:  14641174     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Following reports that a VacA+cag+ toxigenic but not a VacA-cag- non-toxigenic Helicobacter pylori strain induced homotypic phagosome fusion in murine macrophages, we addressed that phenomenon in human cells. Mononuclear phagocytes and epitheloid cells were challenged with H. pylori strains of different vacA and cag genotypes and with VacA- and Cag- isogenic mutants, and chased in the absence or presence of signal transduction modulators. Electron microscopy revealed that, in monocytes: (i) homotypic phagosome fusion was frequently induced by all live H. pylori strains investigated but not by exogenous VacA; (ii) phagosomes containing bacteria fused, but not those containing latex beads; (iii) fusion resulted in communal compartments resembling giant multivesicular bodies; and (iv) formation of these compartments was blocked by inhibiting the host cell regulators PI 3-kinase, phospholipase C and p42 MAP kinase. Whereas some internalized bacteria remained viable 1 h after uptake, none survived a 24 h period. In contrast to monocytes, infected epitheloid cells rarely developed communal compartments. In combination, these results demonstrate that, in human monocytes, the H. pylori-induced homotypic phagosome fusion depends on neither the vacuolating cytotoxin VacA nor the cag pathogenicity island of H. pylori and does not result in prolonged intracellular survival.
Authors:
M G Rittig; B Shaw; D P Letley; R J Thomas; R H Argent; J C Atherton
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cellular microbiology     Volume:  5     ISSN:  1462-5814     ISO Abbreviation:  Cell. Microbiol.     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2003-12-03     Completed Date:  2004-03-09     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100883691     Medline TA:  Cell Microbiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  887-99     Citation Subset:  IM    
Affiliation:
Centre for Biochemistry and Cell Biology, Institute of Infections, Immunity and Inflammation, University of Nottingham Meeical School, UK. michael.rittig@nottingham.ac.uk
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / antagonists & inhibitors
Androstadienes / pharmacology
Bacterial Proteins / genetics,  metabolism
Cell Line
Chromones / pharmacology
Colony Count, Microbial
Epithelioid Cells / microbiology*,  ultrastructure
Estrenes / pharmacology
Gene Deletion
Genes, Bacterial / genetics
Helicobacter pylori / genetics,  pathogenicity*
Humans
Microscopy, Electron
Microspheres
Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
Monocytes / microbiology*,  ultrastructure
Morpholines / pharmacology
Mutagenesis, Insertional
Phagosomes / microbiology*,  physiology,  ultrastructure
Pyrrolidinones / pharmacology
Type C Phospholipases / antagonists & inhibitors
Tyrphostins / pharmacology
Chemical
Reg. No./Substance:
0/Androstadienes; 0/Bacterial Proteins; 0/Chromones; 0/Estrenes; 0/Morpholines; 0/PicB protein, Helicobacter pylori; 0/Pyrrolidinones; 0/Tyrphostins; 0/VacA protein, Helicobacter pylori; 112648-68-7/1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; 118409-62-4/AG 127; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; 19545-26-7/wortmannin; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 3.1.4.-/Type C Phospholipases

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