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Leishmania donovani lipophosphoglycan blocks NADPH oxidase assembly at the phagosome membrane.
Lodge, Robert; Diallo, Tamsir O; Descoteaux, Albert.
Affiliation
  • Lodge R; INRS-Institut Armand Frappier and Centre for Host Parasite Interactions, Laval, QC, Canada, H7V 1B7.
Cell Microbiol ; 8(12): 1922-31, 2006 Dec.
Article in En | MEDLINE | ID: mdl-16848789
Phagocytosis of Leishmania donovani promastigotes is characterized by an inhibition of phagolysosome biogenesis mediated by the surface glycolipid lipophosphoglycan (LPG). However, the consequences of this inhibition on macrophage function remain to be determined. In this study, we investigated the impact of LPG-mediated phagosome remodelling on the assembly and function of the NADPH oxidase complex. Phagocytosis of both wild-type and LPG-defective L. donovani promastigotes triggered the release of similar levels of superoxide. However, wild-type promastigotes, but not LPG-defective mutants, inhibited generation of superoxide at the phagosome. Confocal microscopy imaging revealed that the membrane component gp91(phox) and the Rho-family GTPase Rac1 were present on phagosomes containing either wild-type or LPG-defective promastigotes. In contrast, the NADPH oxidase cytosolic components p47(phox) and p67(phox) were excluded from phagosomes in a LPG-dependent fashion. This inhibition is not the consequence of a general defect in the initiation of the NADPH oxidase activation process because both wild-type and LPG-defective promastigotes induced p47(phox) phosphorylation and the formation of complexes containing p47(phox) and p67(phox). Thus, by remodelling their intracellular habitat, L. donovani promastigotes prevent the assembly of a functional phagosomal NADPH oxidase complex, thereby evading an important host innate defence mechanism.
Subject(s)
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Collection: 01-internacional Database: MEDLINE Main subject: Leishmania donovani / Phagosomes / Glycosphingolipids / Macrophages, Peritoneal / NADPH Oxidases Limits: Animals Language: En Journal: Cell Microbiol Journal subject: MICROBIOLOGIA Year: 2006 Document type: Article Country of publication: India
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Collection: 01-internacional Database: MEDLINE Main subject: Leishmania donovani / Phagosomes / Glycosphingolipids / Macrophages, Peritoneal / NADPH Oxidases Limits: Animals Language: En Journal: Cell Microbiol Journal subject: MICROBIOLOGIA Year: 2006 Document type: Article Country of publication: India