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: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4156363?pdf=render |
| _version_ | 1818021318472237056 |
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| author | Katherine N Gibson-Corley Marie M Bockenstedt Huijuan Li Paola M Boggiatto Yashdeep Phanse Christine A Petersen Bryan H Bellaire Douglas E Jones |
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-14T08:17:14Z |
| format | Article |
| id | doaj.art-3f5d39b1152c4f2c8e1e155c221c4cde |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T08:17:14Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3f5d39b1152c4f2c8e1e155c221c4cde2022-12-22T02:04:21ZengPublic 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 |
| 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 |
| title | 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_short | 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 |
| url | http://europepmc.org/articles/PMC4156363?pdf=render |
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