Lipophosphoglycan (LPG) from Leishmania donovani inhibits phagosomal maturation and oxygen redical production in human neutrophils
(English)Manuscript (preprint) (Other academic)
Lipophosphoglycan (LPG) is the major surface glycoconjugate on Leishmania donovani promastigotes. LPG inhibits phagosome maturation and is crucial for parasite survival in macrophages. Fusion of vesicles with the phagosome is essential for the formation of a mature phagolysosorne and depolymerization of periphagosomal F-actin is likely a prerequisite for vesicle fusion. In macrophages LPG induces an accumulation of periphagosomal F-actin which is correlated to inhibition of vesicle fusion to the phagosome. In this work we investigated the effects of LPG on phagosome maturation in human neutrophils. We found that ingestion of serum-opsonised, LPG-coated yeast particles induced increased levels of periphagosomal Factin in neutrophils. Phagosome maturation was studied using antibodies to CD63 (azurophil granules), synaptotagmin II (specific granules) and LAMP-1 (specific granules, secretory vesicles, multivesicular bodies/multilaminar compartments). Results showed impaired translocation of all these three markers to phagosomes containing LPG-coated prey. The translocation of the early endosome marker Rab5A to the phagosome was not affected by LPG. The late endosomal marker Rab7 was not found in human neutrophils. Chemiluminescence studies revealed that serum-opsonised, LPG-coated yeast induced less production of reactive oxygen metabolites (ROM) compared to controls and that the production was mainly intracellular.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-84710OAI: oai:DiVA.org:liu-84710DiVA: diva2:561236