Journal article
Differences in human macrophage receptor usage, lysosomal fusion kinetics and survival between logarithmic and metacyclic Leishmania infantum chagasi promastigotes
Cellular microbiology, Vol.11(12), pp.1827-1841
12/2009
DOI: 10.1111/j.1462-5822.2009.01374.x
PMCID: PMC2788030
PMID: 19702651
Abstract
The obligate intracellular protozoan, Leishmania infantum chagasi (Lic) undergoes receptor-mediated phagocytosis by macrophages followed by a transient delay in phagolysosome maturation. We found differences in the pathway through which virulent Lic metacyclic promastigotes or avirulent logarithmic promastigotes are phagocytosed by human monocyte-derived macrophages (MDMs). Both logarithmic and metacyclic promastigotes entered MDMs through a compartment lined by the third complement receptor (CR3). In contrast, many logarithmic promastigotes entered through vacuoles lined by mannose receptors (MR) whereas most metacyclic promastigotes did not (P < 0.005). CR3-positive vacuoles containing metacyclic promastigotes stained for caveolin-1 protein, suggesting CR3 localizes in caveolae during phagocytosis. Following entry, the kinetics of phagolysosomal maturation and intracellular survival also differed. Vacuoles containing metacyclic parasites did not accumulate lysosome-associated membrane protein-1 (LAMP-1) at early times after phagocytosis, whereas vacuoles with logarithmic promastigotes did. MDMs phagocytosed greater numbers of logarithmic than metacyclic promastigotes, yet metacyclics ultimately replicated intracellularly with greater efficiency. These data suggest that virulent metacyclic Leishmania promastigotes fail to ligate macrophage MR, and enter through a path that ultimately enhances intracellular survival. The relatively quiescent entry of virulent Leishmania spp. into macrophages may be accounted for by the ability of metacyclic promastigotes to selectively bypass deleterious entry pathways.
Details
- Title: Subtitle
- Differences in human macrophage receptor usage, lysosomal fusion kinetics and survival between logarithmic and metacyclic Leishmania infantum chagasi promastigotes
- Creators
- Norikiyo Ueno - Department of Microbiology, the University of Iowa, Iowa City, IA, USACarol L BrattNilda E RodriguezMary E Wilson
- Resource Type
- Journal article
- Publication Details
- Cellular microbiology, Vol.11(12), pp.1827-1841
- DOI
- 10.1111/j.1462-5822.2009.01374.x
- PMID
- 19702651
- PMCID
- PMC2788030
- NLM abbreviation
- Cell Microbiol
- ISSN
- 1462-5822
- eISSN
- 1462-5822
- Publisher
- England
- Grant note
- R01 AI045540 / NIAID NIH HHS R01 AI045540-07 / NIAID NIH HHS R01 AI059451 / NIAID NIH HHS AI059451 / NIAID NIH HHS R01 AI067874 / NIAID NIH HHS AI067874 / NIAID NIH HHS AI045540 / NIAID NIH HHS
- Language
- English
- Date published
- 12/2009
- Academic Unit
- Microbiology and Immunology; International Programs; Epidemiology; Internal Medicine
- Record Identifier
- 9984001150302771
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