Dynamic life and death interactions between Mycobacterium smegmatis and J774 macrophages
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Date
Authors
Anes, E.
Peyron, P.
Staali, L.
Jordao, L.
Gutierrez, M. G.
Kress, H.
Hagedorn, M.
Maridonneau-Parini, I.
Skinner, M. A.
Wildeman, A. G.
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Abstract
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peer-reviewed
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Cell Microbiol
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Description
After internalization into macrophages non-pathogenic mycobacteria are killed within phagosomes. Pathogenic mycobacteria can block phagosome maturation and grow inside phagosomes but under some conditions can also be killed by macrophages. Killing mechanisms are poorly understood, although phago-lysosome fusion and nitric oxide (NO) production are implicated. We initiated a systematic analysis addressing how macrophages kill 'non-pathogenic'Mycobacterium smegmatis. This system was dynamic, involving periods of initial killing, then bacterial multiplication, followed by two additional killing stages. NO synthesis represented the earliest killing factor but its synthesis stopped during the first killing period. Phagosome actin assembly and fusion with late endocytic organelles coincided with the first and last killing phase, while recycling of phagosome content and membrane coincided with bacterial growth. Phagosome acidification and acquisition of the vacuolar (V) ATPase followed a different pattern coincident with later killing phases. Moreover, V-ATPase localized to vesicles distinct from classical late endosomes and lysosomes. Map kinase p38 is a crucial regulator of all processes investigated, except NO synthesis, that facilitated the host for some functions while being usurped by live bacteria for others. A mathematical model argues that periodic high and low cellular killing activity is more effective than is a continuous process.
Description
Keywords
Actins/analysis/metabolism, Animals, Cell Death, Cell Line, Cell Survival, Endosomes/physiology, Enzyme Inhibitors/pharmacology, Hydrogen-Ion Concentration, Lysosomes/enzymology/physiology, Macrolides/pharmacology, Macrophages/cytology/*microbiology/*physiology, Mice, *Microbial Viability, Models, Theoretical, Mycobacterium smegmatis/drug effects/pathogenicity/*physiology, Nitric Oxide/metabolism, Nitric Oxide Synthase Type II/physiology, Organelles/physiology, Phagosomes/chemistry/physiology, p38 Mitogen-Activated Protein Kinases/physiology
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Citation
Link
http://www.ncbi.nlm.nih.gov/pubmed/16681836
http://onlinelibrary.wiley.com/store/10.1111/j.1462-5822.2005.00675.x/asset/j.1462-5822.2005.00675.x.pdf?v=1&t=h0ko6e68&s=b1680e63a2bca955d89aa676aac63ffa781338e2
http://onlinelibrary.wiley.com/store/10.1111/j.1462-5822.2005.00675.x/asset/j.1462-5822.2005.00675.x.pdf?v=1&t=h0ko6e68&s=b1680e63a2bca955d89aa676aac63ffa781338e2
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en
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Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής