Journal article
Complement receptor 3 mediates ruffle-like, actin-rich aggregates during phagocytosis of Leishmania infantum metacyclics
Experimental parasitology, Vol.220, pp.107968-107968
01/2021
DOI: 10.1016/j.exppara.2020.107968
PMCID: PMC7750307
PMID: 32781093
Abstract
The parasitic protozoan Leishmania infantum resides primarily in macrophages throughout mammalian infection. Infection is initiated by deposition of the metacyclic promastigote into the dermis of a mammalian host by the sand fly vector. Promastigotes enter macrophages by ligating surface receptors such as complement receptor 3 (CR3), inducing phagocytosis of the parasite. At the binding site of metacyclic promastigotes, we observed large asymmetrical aggregates of macrophage membrane with underlying actin, resembling membrane ruffles. Actin accumulation was observed at the point of initial contact, before phagosome formation and accumulation of peri-phagosomal actin. Ruffle-like structures did not form during phagocytosis of attenuated promastigotes or during phagocytosis of the intracellular amastigote form of L. infantum. Entry of promastigotes through massive actin accumulation was associated with a subsequent delay in fusion of the parasitophorous vacuole (PV) with the lysosomal markers LAMP-1 and Cathepsin D. Actin accumulation was also associated with entry through CR3, since macrophages from CD11b knockout (KO) mice did not form massive aggregates of actin during phagocytosis of metacyclic promastigotes. Furthermore, intracellular survival of L. infantum was significantly decreased in CD11b KO compared to wild type macrophages, although entry rates were similar. We conclude that both promastigote virulence and host cell CR3 are needed for the formation of ruffle-like membrane structures at the site of metacyclic promastigote phagocytosis, and that formation of actin-rich aggregates during entry correlates with the intracellular survival of virulent promastigotes.
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•Uptake of L.infantum induced ruffle-like structures at the macrophage membrane.•L. infantum entry through ruffle-like structures is stage- and virulence-dependent.•Actin-rich, ruffle-like structures were dependent on complement receptor 3 (CR3).
Details
- Title: Subtitle
- Complement receptor 3 mediates ruffle-like, actin-rich aggregates during phagocytosis of Leishmania infantum metacyclics
- Creators
- Upasna Gaur Dixit - University of IowaNilda E. Rodríguez - University of Northern IowaRachel Polando - University of Notre DameMary Ann McDowell - University of Notre DameMary E. Wilson - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Experimental parasitology, Vol.220, pp.107968-107968
- DOI
- 10.1016/j.exppara.2020.107968
- PMID
- 32781093
- PMCID
- PMC7750307
- NLM abbreviation
- Exp Parasitol
- ISSN
- 0014-4894
- eISSN
- 1090-2449
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000002, name: U. S. National Institutes of Health, award: T32AI007511, R01 TW 010500, AI045540, R01AI056242; DOI: 10.13039/100000738, name: Department of Veterans’ Affairs, award: I01 BX001983, I01 BX000536; DOI: 10.13039/100000968, name: American Heart Association, award: 0435333Z; DOI: 10.13039/100011654, name: University of Northern Iowa College of Humanities, Arts and Sciences
- Language
- English
- Date published
- 01/2021
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; International Programs; Epidemiology; Internal Medicine
- Record Identifier
- 9984297325302771
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