Journal article
Evidence that Leishmania donovani utilizes a mannose receptor on human mononuclear phagocytes to establish intracellular parasitism
The Journal of immunology (1950), Vol.136(12), pp.4681-4688
06/15/1986
DOI: 10.4049/jimmunol.136.12.4681
PMID: 3711662
Abstract
The pathogenic protozoan Leishmania donovani must gain entrance into mononuclear phagocytes to successfully parasitize man. The parasite's extra-cellular promastigote stage is ingested by human peripheral blood monocytes or monocyte-derived macrophages in the absence of serum, in a manner characteristic of receptor-mediated endocytosis. We have found remarkable similarities between the macrophage receptor(s) for promastigotes and a previously characterized eucaryotic receptor system, the mannose/fucose receptor (MFR), that mediates the binding of zymosan particles and mannose- or fucose-terminal glycoconjugates to macrophages. Ingestion of promastigotes by monocyte-derived macrophages was inhibited by several MFR ligands. Mannan (2.5 mg/ml) decreased ingestion by 63.7% (p less than 0.001), and the neoglycoproteins mannose-BSA and fucose-BSA (20 micrograms/ml) inhibited parasite ingestion by 46.5% and 39.6%, respectively (p less than 0.04). In contrast, promastigote ingestion by monocytes was unaffected by MFR ligands. These results are consistent with reports that MFR activity is present in monocyte-derived macrophages but not in monocytes. Furthermore, attachment of promastigotes to macrophages, assessed by using cytochalasin D to prevent phagocytosis, was reduced 49.8% by mannan. Reorientation of the MFR to the ventral surface of the cell was achieved by plating macrophages onto mannan-coated coverslips, reducing MFR activity on the exposed cell surface by 94% as assessed by binding of 125I-mannose-BSA. Under these conditions, ingestion of promastigotes was inhibited by 71.4% (p less than 0.006). Internalization of the MFR by exposure of macrophages to zymosan before infection with promastigotes resulted in a 62.3% decrease in parasite ingestion (p less than 0.006). Additionally NH4Cl, a weak lysosomotropic base that impairs MFR recycling, decreased macrophage ingestion of promastigotes by 38.2% (p less than 0.03, 30 mM NH4Cl). Subinhibitory concentrations of NH4Cl (10 mM) and of mannan (0.25 mg/ml) together inhibited parasite ingestion by 76.4% (p less than 0.002). These studies suggest that L. donovani promastigotes may utilize a receptor system on human monocyte-derived macrophages, the MFR, to efficiently parasitize the human host.
Details
- Title: Subtitle
- Evidence that Leishmania donovani utilizes a mannose receptor on human mononuclear phagocytes to establish intracellular parasitism
- Creators
- Mary E WilsonRichard D Pearson
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.136(12), pp.4681-4688
- Publisher
- United States
- DOI
- 10.4049/jimmunol.136.12.4681
- PMID
- 3711662
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- T32AI07046 / NIAID NIH HHS AI-18482 / NIAID NIH HHS
- Language
- English
- Date published
- 06/15/1986
- Academic Unit
- Microbiology and Immunology; International Programs; Epidemiology; Internal Medicine
- Record Identifier
- 9984001115102771
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