The Ultrastructure of the Parasitophorous Vacuole Formed by Leishmania Major

Abstract

Protozoan parasites of Leishmania spp. invade macrophages as promastigotes and differentiate into replicative amastigotes within parasitophorous vacuoles. Infection of inbred strains of mice with Leishmania major is a well-studied model of the mammalian immune response to Leishmania species, but the ultrastructure and biochemical properties of the parasitophorous vacuole occupied by this parasite have been best characterized for other species of Leishmania. We examined the parasitophorous vacuole occupied by L. major in lymph nodes of infected mice and in bone marrow-derived macrophages infected in vitro. At all time points after infection, single L. major amastigotes were wrapped tightly by host membrane, suggesting that amastigotes segregate into separate vacuoles during replication. This small, individual vacuole contrasts sharply with the large, communal vacuoles occupied by Leishmania amazonensis. An extensive survey of the literature revealed that the single vacuoles occupied by L. major are characteristic of those formed by Old World species of Leishmania, while New World species of Leishmania form large vacuoles occupied by many amastigotes.

Comparisons of Mutants Lacking the Golgi UDP-Galactose or GDP-Mannose Transporters Establish that Phosphoglycans Are Important for Promastigote but Not Amastigote Virulence in Leishmania major

“…Potentially L. mexicana may synthesize novel glycoconjugates and/or other molecules that fulfill this role in the absence of LPG2. Alternatively, the molecules required for amastigote virulence may differ between the species due to differences in the parasite biology, with one example being the natures of the parasitophorous vacuoles formed by L. mexicana versus L. donovani and L. major (4). The availability of well-characterized mutants of all three species should greatly facilitate the resolution of this important question in the future.…”

“…1A) (12). Additionally, the phosphoglycan [Gal(␤1,4)Man(␣1-PO 4 )] disaccharide-phosphate repeating units (PG repeats) modify a variety of surface and secreted proteins and comprise the major portion of LPG, which contains 15 to 30 PG repeats (21,56,60). Thus, while studies carried out on purified PGs point to important roles such as modulating host signal transduction, inhibiting phagolysosomal fusion, and mediating oxidant resistance (reviewed by in reference 8), the structural similarity among these complex molecules often leads to imprecision in our understanding of their unique and/or overlapping roles in vivo.…”

Possible Effects of Microbial Ecto-Nucleoside Triphosphate Diphosphohydrolases on Host-Pathogen Interactions

“…All of these syndromes have serious sequelae, but visceral leishmaniasis is particularly life-threatening (71). Leishmania replicates inside macrophages within a parasitophorous vacuole, the morphology of which varies between parasite species (23).…”

The Diverse and Dynamic Nature of Leishmania Parasitophorous Vacuoles Studied by Multidimensional Imaging

“…These studies led to the characterization of the biochemical and functional features of Leishmania PVs, which may not apply to the majority of Leishmania species studied that are lodged in tight PVs and assumed to undergo fission as parasites divide [21], [22]. The accessibility of particles, macromolecules, and probes to these tight-fitting PVs and the identification of their contents are hindered by the limited vacuolar space available between the parasites and their PV membranes.…”