An in vitro model of antibody-enhanced killing of the intracellular parasite Leishmania amazonensis.
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...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2014-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4156363?pdf=render |
id |
doaj-3f5d39b1152c4f2c8e1e155c221c4cde |
---|---|
record_format |
Article |
spelling |
doaj-3f5d39b1152c4f2c8e1e155c221c4cde2020-11-25T01:00:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10642610.1371/journal.pone.0106426An in vitro model of antibody-enhanced killing of the intracellular parasite Leishmania amazonensis.Katherine N Gibson-CorleyMarie M BockenstedtHuijuan LiPaola M BoggiattoYashdeep PhanseChristine A PetersenBryan H BellaireDouglas E JonesFootpad 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.http://europepmc.org/articles/PMC4156363?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Katherine N Gibson-Corley Marie M Bockenstedt Huijuan Li Paola M Boggiatto Yashdeep Phanse Christine A Petersen Bryan H Bellaire Douglas E Jones |
spellingShingle |
Katherine N Gibson-Corley Marie M Bockenstedt Huijuan Li Paola M Boggiatto Yashdeep Phanse Christine A Petersen Bryan H Bellaire Douglas E Jones An in vitro model of antibody-enhanced killing of the intracellular parasite Leishmania amazonensis. PLoS ONE |
author_facet |
Katherine N Gibson-Corley Marie M Bockenstedt Huijuan Li Paola M Boggiatto Yashdeep Phanse Christine A Petersen Bryan H Bellaire Douglas E Jones |
author_sort |
Katherine N Gibson-Corley |
title |
An in vitro model of antibody-enhanced killing of the intracellular parasite Leishmania amazonensis. |
title_short |
An in vitro model of antibody-enhanced killing of the intracellular parasite Leishmania amazonensis. |
title_full |
An in vitro model of antibody-enhanced killing of the intracellular parasite Leishmania amazonensis. |
title_fullStr |
An in vitro model of antibody-enhanced killing of the intracellular parasite Leishmania amazonensis. |
title_full_unstemmed |
An in vitro model of antibody-enhanced killing of the intracellular parasite Leishmania amazonensis. |
title_sort |
in vitro model of antibody-enhanced killing of the intracellular parasite leishmania amazonensis. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC4156363?pdf=render |
work_keys_str_mv |
AT katherinengibsoncorley aninvitromodelofantibodyenhancedkillingoftheintracellularparasiteleishmaniaamazonensis AT mariembockenstedt aninvitromodelofantibodyenhancedkillingoftheintracellularparasiteleishmaniaamazonensis AT huijuanli aninvitromodelofantibodyenhancedkillingoftheintracellularparasiteleishmaniaamazonensis AT paolamboggiatto aninvitromodelofantibodyenhancedkillingoftheintracellularparasiteleishmaniaamazonensis AT yashdeepphanse aninvitromodelofantibodyenhancedkillingoftheintracellularparasiteleishmaniaamazonensis AT christineapetersen aninvitromodelofantibodyenhancedkillingoftheintracellularparasiteleishmaniaamazonensis AT bryanhbellaire aninvitromodelofantibodyenhancedkillingoftheintracellularparasiteleishmaniaamazonensis AT douglasejones aninvitromodelofantibodyenhancedkillingoftheintracellularparasiteleishmaniaamazonensis AT katherinengibsoncorley invitromodelofantibodyenhancedkillingoftheintracellularparasiteleishmaniaamazonensis AT mariembockenstedt invitromodelofantibodyenhancedkillingoftheintracellularparasiteleishmaniaamazonensis AT huijuanli invitromodelofantibodyenhancedkillingoftheintracellularparasiteleishmaniaamazonensis AT paolamboggiatto invitromodelofantibodyenhancedkillingoftheintracellularparasiteleishmaniaamazonensis AT yashdeepphanse invitromodelofantibodyenhancedkillingoftheintracellularparasiteleishmaniaamazonensis AT christineapetersen invitromodelofantibodyenhancedkillingoftheintracellularparasiteleishmaniaamazonensis AT bryanhbellaire invitromodelofantibodyenhancedkillingoftheintracellularparasiteleishmaniaamazonensis AT douglasejones invitromodelofantibodyenhancedkillingoftheintracellularparasiteleishmaniaamazonensis |
_version_ |
1725213290133454848 |