Journal article
Attenuation of Leishmania infantum chagasi Metacyclic Promastigotes by Sterol Depletion
Infection and immunity, Vol.81(7), pp.2507-2517
07/2013
DOI: 10.1128/IAI.00214-13
PMCID: PMC3697599
PMID: 23630964
Abstract
The infectious metacyclic promastigotes of
Leishmania
protozoa establish infection in a mammalian host after they are deposited into the dermis by a sand fly vector. Several
Leishmania
virulence factors promote infection, including the glycosylphosphatidylinositol membrane-anchored major surface protease (MSP). Metacyclic
Leishmania infantum chagasi
promastigotes were treated with methyl-beta-cyclodextrin (MβCD), a sterol-chelating reagent, causing a 3-fold reduction in total cellular sterols as well as enhancing MSP release without affecting parasite viability
in vitro
. MβCD-treated promastigotes were more susceptible to complement-mediated lysis than untreated controls and reduced the parasite load 3-fold when inoculated into BALB/c mice. Paradoxically, MβCD-treated promastigotes caused a higher initial
in vitro
infection rate in human or murine macrophages than untreated controls, although their intracellular multiplication was hindered upon infection establishment. There was a corresponding larger amount of covalently bound C3b than iC3b on the parasite surfaces of MβCD-treated promastigotes exposed to healthy human serum
in vitro
, as well as loss of MSP, a protease that enhances C3b cleavage to iC3b. Mass spectrometry showed that MβCD promotes the release of proteins into the extracellular medium, including both MSP and MSP-like protein (MLP), from virulent metacyclic promastigotes. These data support the hypothesis that plasma membrane sterols are important for the virulence of
Leishmania
protozoa at least in part through retention of membrane virulence proteins.
Details
- Title: Subtitle
- Attenuation of Leishmania infantum chagasi Metacyclic Promastigotes by Sterol Depletion
- Creators
- Chaoqun Yao - Iowa City VA Medical Center, Iowa City, Iowa, USAUpasna Gaur Dixit - Departments of Internal MedicineJason H Barker - Departments of Internal MedicineLynn M Teesch - University of Iowa, Iowa City, Iowa, USALaurie Love-Homan - Departments of Internal MedicineJohn E Donelson - BiochemistryMary E Wilson - Iowa City VA Medical Center, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- Infection and immunity, Vol.81(7), pp.2507-2517
- Publisher
- American Society for Microbiology; 1752 N St., N.W., Washington, DC
- DOI
- 10.1128/IAI.00214-13
- PMID
- 23630964
- PMCID
- PMC3697599
- ISSN
- 0019-9567
- eISSN
- 1098-5522
- Language
- English
- Date published
- 07/2013
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; International Programs; Epidemiology; Core Research Facilities; Biochemistry and Molecular Biology; Medicine Administration; Internal Medicine
- Record Identifier
- 9984001230502771
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