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IL-4Rα-Associated Antigen Processing by B Cells Promotes Immunity in Nippostrongylus brasiliensis Infection

In this study, B cell function in protective T(H)2 immunity against N. brasiliensis infection was investigated. Protection against secondary infection depended on IL-4Rα and IL-13; but not IL-4. Protection did not associate with parasite specific antibody responses. Re-infection of B cell-specific I...

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Autores principales: Horsnell, William G. C., Darby, Matthew G., Hoving, Jennifer C., Nieuwenhuizen, Natalie, McSorley, Henry J., Ndlovu, Hlumani, Bobat, Saeeda, Kimberg, Matti, Kirstein, Frank, Cutler, Anthony J., DeWals, Benjamin, Cunningham, Adam F., Brombacher, Frank
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812011/
https://www.ncbi.nlm.nih.gov/pubmed/24204255
http://dx.doi.org/10.1371/journal.ppat.1003662
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author Horsnell, William G. C.
Darby, Matthew G.
Hoving, Jennifer C.
Nieuwenhuizen, Natalie
McSorley, Henry J.
Ndlovu, Hlumani
Bobat, Saeeda
Kimberg, Matti
Kirstein, Frank
Cutler, Anthony J.
DeWals, Benjamin
Cunningham, Adam F.
Brombacher, Frank
author_facet Horsnell, William G. C.
Darby, Matthew G.
Hoving, Jennifer C.
Nieuwenhuizen, Natalie
McSorley, Henry J.
Ndlovu, Hlumani
Bobat, Saeeda
Kimberg, Matti
Kirstein, Frank
Cutler, Anthony J.
DeWals, Benjamin
Cunningham, Adam F.
Brombacher, Frank
author_sort Horsnell, William G. C.
collection PubMed
description In this study, B cell function in protective T(H)2 immunity against N. brasiliensis infection was investigated. Protection against secondary infection depended on IL-4Rα and IL-13; but not IL-4. Protection did not associate with parasite specific antibody responses. Re-infection of B cell-specific IL-4Rα(−/−) mice resulted in increased worm burdens compared to control mice, despite their equivalent capacity to control primary infection. Impaired protection correlated with reduced lymphocyte IL-13 production and B cell MHC class II and CD86 surface expression. Adoptive transfer of in vivo N. brasiliensis primed IL-4Rα expressing B cells into naïve BALB/c mice, but not IL-4Rα or IL-13 deficient B cells, conferred protection against primary N. brasiliensis infection. This protection required MHC class II compatibility on B cells suggesting cognate interactions by B cells with CD4(+) T cells were important to co-ordinate immunity. Furthermore, the rapid nature of these protective effects by B cells suggested non-BCR mediated mechanisms, such as via Toll Like Receptors, was involved, and this was supported by transfer experiments using antigen pulsed Myd88(−/−) B cells. These data suggest TLR dependent antigen processing by IL-4Rα-responsive B cells producing IL-13 contribute significantly to CD4(+) T cell-mediated protective immunity against N. brasiliensis infection.
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spelling pubmed-38120112013-11-07 IL-4Rα-Associated Antigen Processing by B Cells Promotes Immunity in Nippostrongylus brasiliensis Infection Horsnell, William G. C. Darby, Matthew G. Hoving, Jennifer C. Nieuwenhuizen, Natalie McSorley, Henry J. Ndlovu, Hlumani Bobat, Saeeda Kimberg, Matti Kirstein, Frank Cutler, Anthony J. DeWals, Benjamin Cunningham, Adam F. Brombacher, Frank PLoS Pathog Research Article In this study, B cell function in protective T(H)2 immunity against N. brasiliensis infection was investigated. Protection against secondary infection depended on IL-4Rα and IL-13; but not IL-4. Protection did not associate with parasite specific antibody responses. Re-infection of B cell-specific IL-4Rα(−/−) mice resulted in increased worm burdens compared to control mice, despite their equivalent capacity to control primary infection. Impaired protection correlated with reduced lymphocyte IL-13 production and B cell MHC class II and CD86 surface expression. Adoptive transfer of in vivo N. brasiliensis primed IL-4Rα expressing B cells into naïve BALB/c mice, but not IL-4Rα or IL-13 deficient B cells, conferred protection against primary N. brasiliensis infection. This protection required MHC class II compatibility on B cells suggesting cognate interactions by B cells with CD4(+) T cells were important to co-ordinate immunity. Furthermore, the rapid nature of these protective effects by B cells suggested non-BCR mediated mechanisms, such as via Toll Like Receptors, was involved, and this was supported by transfer experiments using antigen pulsed Myd88(−/−) B cells. These data suggest TLR dependent antigen processing by IL-4Rα-responsive B cells producing IL-13 contribute significantly to CD4(+) T cell-mediated protective immunity against N. brasiliensis infection. Public Library of Science 2013-10-24 /pmc/articles/PMC3812011/ /pubmed/24204255 http://dx.doi.org/10.1371/journal.ppat.1003662 Text en © 2013 Horsnell et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Horsnell, William G. C.
Darby, Matthew G.
Hoving, Jennifer C.
Nieuwenhuizen, Natalie
McSorley, Henry J.
Ndlovu, Hlumani
Bobat, Saeeda
Kimberg, Matti
Kirstein, Frank
Cutler, Anthony J.
DeWals, Benjamin
Cunningham, Adam F.
Brombacher, Frank
IL-4Rα-Associated Antigen Processing by B Cells Promotes Immunity in Nippostrongylus brasiliensis Infection
title IL-4Rα-Associated Antigen Processing by B Cells Promotes Immunity in Nippostrongylus brasiliensis Infection
title_full IL-4Rα-Associated Antigen Processing by B Cells Promotes Immunity in Nippostrongylus brasiliensis Infection
title_fullStr IL-4Rα-Associated Antigen Processing by B Cells Promotes Immunity in Nippostrongylus brasiliensis Infection
title_full_unstemmed IL-4Rα-Associated Antigen Processing by B Cells Promotes Immunity in Nippostrongylus brasiliensis Infection
title_short IL-4Rα-Associated Antigen Processing by B Cells Promotes Immunity in Nippostrongylus brasiliensis Infection
title_sort il-4rα-associated antigen processing by b cells promotes immunity in nippostrongylus brasiliensis infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812011/
https://www.ncbi.nlm.nih.gov/pubmed/24204255
http://dx.doi.org/10.1371/journal.ppat.1003662
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