title: Trafficking of Leishmania donovani promastigotes in non-lytic compartments in neutrophils enables the subsequent transfer of parasites to macrophages.
abstract: Inoculation of Leishmania (L.) spp. promastigotes in the dermis of mammals by blood-feeding sand flies can be accompanied by the rapid recruitment of neutrophils, inflammatory monocytes and dendritic cells. Despite the presence of these lytic leucocytes, parasitism is efficiently established. We show here that Leishmania donovani promastigotes are targeted to two different compartments in neutrophils. The compartments harbouring either damaged or non-damaged parasites were characterized at the electron microscopy (EM) level using the glucose 6-phosphatase cytochemistry and endosome-phagosome fusion assays. One involves the contribution of lysosomes leading to the formation of highly lytic compartments where parasites are rapidly degraded. The other is lysosome-independent and involves the contribution of a compartment displaying some features of the endoplasmic reticulum (ER) where parasites are protected from degradation. Using genetically modified parasites, we show that the promastigote surface lipophosphoglycan (LPG) is required to inhibit lysosome fusion and maintain parasites in neutrophil compartments displaying ER features. L. donovani-harbouring neutrophils that eventually enter apoptosis can be phagocytosed by macrophages enabling the stealth entry of parasites into their final replicative host cells. Thus, the ability of L. donovani to avoid trafficking into lysosomes-derived compartments in short-lived neutrophils constitutes a key process for the subsequent establishment of long-term parasitism.
authors.affiliation: Département de Pathologie et Biologie Cellulaire, Université de Montréal, C.P.6128, Succ. Centre ville, Montreal, Canada. pgueirar@pasteur.fr
authors.forename: Pascale
authors.initials: P
authors.lastname: Gueirard
authors.forename: Annie
authors.initials: A
authors.lastname: Laplante
authors.forename: Christiane
authors.initials: C
authors.lastname: Rondeau
authors.forename: Geneviève
authors.initials: G
authors.lastname: Milon
authors.forename: Michel
authors.initials: M
authors.lastname: Desjardins
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002478:Cells, Cultured; D004285:Dogs; D011992:Endosomes / Q000737:chemistry / Q000469:parasitology* / Q000648:ultrastructure; D006028:Glycosphingolipids / Q000502:physiology; D007893:Leishmania donovani / Q000276:immunology*; D008247:Lysosomes / Q000737:chemistry / Q000469:parasitology* / Q000648:ultrastructure; D008264:Macrophages / Q000469:parasitology*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009504:Neutrophils / Q000737:chemistry / Q000469:parasitology* / Q000648:ultrastructure
chemical_list: D006028:Glycosphingolipids; C008290:lipophosphonoglycan