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Abortive T Follicular Helper Development Is Associated with a Defective Humoral Response in Leishmania infantum-Infected Macaques

Silvestri, Guido, Rodrigues, Vasco, Laforge, Mireille, Campillo-Gimenez, Laure, Soundaramourty, Calaiselvy, Oliveira, Ana, Dinis-Oliveira, Ricardo Jorge, Ouaissi, Ali, Cordeiro-da-Silva, Anabela, Silvestre, Ricardo, and others. (2014) Abortive T Follicular Helper Development Is Associated with a Defective Humoral Response in Leishmania infantum-Infected Macaques. PLoS Pathogens, 10 (4). Article Number e1004096. ISSN 1553-7374. (doi:10.1371/journal.ppat.1004096) (KAR id:98383)

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Official URL:
https://doi.org/10.1371/journal.ppat.1004096

Abstract

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.

Item Type: Article
DOI/Identification number: 10.1371/journal.ppat.1004096
Subjects: R Medicine
Divisions: Divisions > Division of Natural Sciences > Kent and Medway Medical School
Depositing User: Ana Oliveira
Date Deposited: 27 Nov 2022 16:15 UTC
Last Modified: 02 Dec 2022 09:43 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/98383 (The current URI for this page, for reference purposes)
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