Abortive T follicular helper development is associated with a defective humoral response in Leishmania infantum-infected macaques.

Leishmania infantum causes a chronic infectious disease named visceral leishmaniasis (VL). We employed a non-human primate model to monitor immune parameters over time and gain new insights into the disease. Rhesus macaques were infected with L. infantum and the T helper and B cell immunological pro...

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Main Authors: Vasco Rodrigues, Mireille Laforge, Laure Campillo-Gimenez, Calaiselvy Soundaramourty, Ana Correia-de-Oliveira, Ricardo Jorge Dinis-Oliveira, Ali Ouaissi, Anabela Cordeiro-da-Silva, Ricardo Silvestre, Jérôme Estaquier
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-04-01
Series:PLoS Pathogens
Online Access:http://europepmc.org/articles/PMC4005728?pdf=render
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author Vasco Rodrigues
Mireille Laforge
Laure Campillo-Gimenez
Calaiselvy Soundaramourty
Ana Correia-de-Oliveira
Ricardo Jorge Dinis-Oliveira
Ali Ouaissi
Anabela Cordeiro-da-Silva
Ricardo Silvestre
Jérôme Estaquier
author_facet Vasco Rodrigues
Mireille Laforge
Laure Campillo-Gimenez
Calaiselvy Soundaramourty
Ana Correia-de-Oliveira
Ricardo Jorge Dinis-Oliveira
Ali Ouaissi
Anabela Cordeiro-da-Silva
Ricardo Silvestre
Jérôme Estaquier
author_sort Vasco Rodrigues
collection DOAJ
description Leishmania infantum causes a chronic infectious disease named visceral leishmaniasis (VL). We employed a non-human primate model to monitor immune parameters over time and gain new insights into the disease. Rhesus macaques were infected with L. infantum and the T helper and B cell immunological profiles characterized during acute and chronic phases of infection. Parasite detection in visceral compartments during the acute phase was associated with differentiation of effector memory CD4 T cells and increased levels of Th1 transcripts. At the chronic phase, parasites colonized novel lymphoid niches concomitant with increased expression of IL10. Despite the occurrence of hypergammaglobulinemia, the production of parasite-specific IgG was poor, being confined to the acute phase and positively correlated with the frequency of an activated memory splenic B cell population. We noticed the expansion of a splenic CD4 T cell population expressing CXCR5 and Bcl-6 during acute infection that was associated with the differentiation of the activated memory B cell population. Moreover, the number of splenic germinal centers peaked at one month after infection, hence paralleling the production of specific IgG. However, at chronic infection these populations contracted impacting the production of parasite-specific IgG. Our study provides new insights into the immune events taking place in a physiologically relevant host and a mechanistic basis for the inefficient humoral response during VL.
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spelling doaj.art-6eee153a98b8418fb8c4b6d0c6a467542022-12-21T22:58:08ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-04-01104e100409610.1371/journal.ppat.1004096Abortive T follicular helper development is associated with a defective humoral response in Leishmania infantum-infected macaques.Vasco RodriguesMireille LaforgeLaure Campillo-GimenezCalaiselvy SoundaramourtyAna Correia-de-OliveiraRicardo Jorge Dinis-OliveiraAli OuaissiAnabela Cordeiro-da-SilvaRicardo SilvestreJérôme EstaquierLeishmania infantum causes a chronic infectious disease named visceral leishmaniasis (VL). We employed a non-human primate model to monitor immune parameters over time and gain new insights into the disease. Rhesus macaques were infected with L. infantum and the T helper and B cell immunological profiles characterized during acute and chronic phases of infection. Parasite detection in visceral compartments during the acute phase was associated with differentiation of effector memory CD4 T cells and increased levels of Th1 transcripts. At the chronic phase, parasites colonized novel lymphoid niches concomitant with increased expression of IL10. Despite the occurrence of hypergammaglobulinemia, the production of parasite-specific IgG was poor, being confined to the acute phase and positively correlated with the frequency of an activated memory splenic B cell population. We noticed the expansion of a splenic CD4 T cell population expressing CXCR5 and Bcl-6 during acute infection that was associated with the differentiation of the activated memory B cell population. Moreover, the number of splenic germinal centers peaked at one month after infection, hence paralleling the production of specific IgG. However, at chronic infection these populations contracted impacting the production of parasite-specific IgG. Our study provides new insights into the immune events taking place in a physiologically relevant host and a mechanistic basis for the inefficient humoral response during VL.http://europepmc.org/articles/PMC4005728?pdf=render
spellingShingle Vasco Rodrigues
Mireille Laforge
Laure Campillo-Gimenez
Calaiselvy Soundaramourty
Ana Correia-de-Oliveira
Ricardo Jorge Dinis-Oliveira
Ali Ouaissi
Anabela Cordeiro-da-Silva
Ricardo Silvestre
Jérôme Estaquier
Abortive T follicular helper development is associated with a defective humoral response in Leishmania infantum-infected macaques.
PLoS Pathogens
title Abortive T follicular helper development is associated with a defective humoral response in Leishmania infantum-infected macaques.
title_full Abortive T follicular helper development is associated with a defective humoral response in Leishmania infantum-infected macaques.
title_fullStr Abortive T follicular helper development is associated with a defective humoral response in Leishmania infantum-infected macaques.
title_full_unstemmed Abortive T follicular helper development is associated with a defective humoral response in Leishmania infantum-infected macaques.
title_short Abortive T follicular helper development is associated with a defective humoral response in Leishmania infantum-infected macaques.
title_sort abortive t follicular helper development is associated with a defective humoral response in leishmania infantum infected macaques
url http://europepmc.org/articles/PMC4005728?pdf=render
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