An in vitro model of antibody-enhanced killing of the intracellular parasite Leishmania amazonensis

Katherine N Gibson-Corley; Marie M Bockenstedt; Huijuan Li; Paola M Boggiatto; Yashdeep Phanse; Christine A Petersen; Bryan H Bellaire; Douglas E Jones

doi:10.1371/journal.pone.0106426

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An in vitro model of antibody-enhanced killing of the intracellular parasite Leishmania amazonensis

Journal article

Open access

Peer reviewed

An in vitro model of antibody-enhanced killing of the intracellular parasite Leishmania amazonensis

Katherine N Gibson-Corley, Marie M Bockenstedt, Huijuan Li, Paola M Boggiatto, Yashdeep Phanse, Christine A Petersen, Bryan H Bellaire and Douglas E Jones

PloS one, Vol.9(9), pp.e106426-e106426

2014

DOI: 10.1371/journal.pone.0106426

PMCID: PMC4156363

PMID: 25191842

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Abstract

Footpad infection of C3HeB/FeJ mice with Leishmania amazonensis leads to chronic lesions accompanied by large parasite loads. Co-infecting these animals with L. major leads to induction of an effective Th1 immune response that can resolve these lesions. This cross-protection can be recapitulated in vitro by using immune cells from L. major-infected animals to effectively activate L. amazonensis-infected macrophages to kill the parasite. We have shown previously that the B cell population and their IgG2a antibodies are required for effective cross-protection. Here we demonstrate that, in contrast to L. major, killing L. amazonensis parasites is dependent upon FcRγ common-chain and NADPH oxidase-generated superoxide from infected macrophages. Superoxide production coincided with killing of L. amazonensis at five days post-activation, suggesting that opsonization of the parasites was not a likely mechanism of the antibody response. Therefore we tested the hypothesis that non-specific immune complexes could provide a mechanism of FcRγ common-chain/NADPH oxidase dependent parasite killing. Macrophage activation in response to soluble IgG2a immune complexes, IFN-γ and parasite antigen was effective in significantly reducing the percentage of macrophages infected with L. amazonensis. These results define a host protection mechanism effective during Leishmania infection and demonstrate for the first time a novel means by which IgG antibodies can enhance killing of an intracellular pathogen.

Signal Transduction

Antibodies, Protozoan - immunology

NADPH Oxidases - metabolism

Antibody-Dependent Cell Cytotoxicity - immunology

Leishmaniasis, Cutaneous - immunology

Phosphatidylinositol 3-Kinases

Receptors, IgG - metabolism

Macrophage Activation

Mice, Knockout

Macrophages - parasitology

Macrophages - metabolism

Animals

Leishmaniasis, Cutaneous - parasitology

Immunoglobulin G - immunology

Superoxides - metabolism

Female

Mice

Antigen-Antibody Complex - immunology

In Vitro Techniques

Leishmania mexicana - immunology

Macrophages - immunology

Disease Models, Animal

Details

Title: Subtitle: An in vitro model of antibody-enhanced killing of the intracellular parasite Leishmania amazonensis
Creators: Katherine N Gibson-Corley - Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America
Marie M Bockenstedt - Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America
Huijuan Li - Iowa State University
Paola M Boggiatto - Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America
Yashdeep Phanse - Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America
Christine A Petersen - Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America
Bryan H Bellaire - Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America
Douglas E Jones - Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America
Resource Type: Journal article
Publication Details: PloS one, Vol.9(9), pp.e106426-e106426
DOI: 10.1371/journal.pone.0106426
PMID: 25191842
PMCID: PMC4156363
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: United States
Grant note: KO8 AI076616 / NIAID NIH HHS
Language: English
Date published: 2014
Academic Unit: Epidemiology; Pathology; Internal Medicine; Ophthalmology and Visual Sciences
Record Identifier: 9983995105102771

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19 Times Cited - Web of Science