Leishmania donovani lipophosphoglycan disrupts phagosome microdomains in J774 macrophages.
Clearance of pathogens by phagocytosis and their killing in phagolysosomes is a key aspect of our innate ability to fight infectious agents. Leishmania parasites have evolved ways to survive and replicate in macrophages by inhibiting phagosome maturation and avoiding the harsh environment of phagolysosomes. We describe here that during this process Leishmania donovani uses a novel strategy involving its surface lipophosphoglycan (LPG), a virulence factor impeding many host functions, to prevent the formation or disrupt lipid microdomains on the phagosome membrane. LPG acts locally on the membrane and requires its repetitive carbohydrate moieties to alter the organization of microdomains. Targeting and disruption of functional foci, where proteins involved in key aspects of phagolysosome biogenesis assemble, is likely to confer a survival advantage to the parasite.
Dermine
Jean-François
JF
Département de Pathologie et Biologie Cellulaire, Université de Montréal, C. P. 6128, Succ. Centre ville, Montreal, H3C 3J7, Canada.
Goyette
Guillaume
G
Houde
Mathieu
M
Turco
Salvatore J
SJ
Desjardins
Michel
M
D000818:Animals; D002460:Cell Line; D006028:Glycosphingolipids / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D007893:Leishmania donovani / Q000378:metabolism*; D050356:Lipid Metabolism; D008264:Macrophages / Q000378:metabolism* / Q000469:parasitology / Q000648:ultrastructure; D021962:Membrane Microdomains / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D010588:Phagosomes / Q000378:metabolism* / Q000648:ultrastructure
D006028:Glycosphingolipids; C008290:lipophosphonoglycan