Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/118193
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dc.creatorRodrigues, V
dc.creatorLaforge, M
dc.creatorCampillo-Gimenez, L
dc.creatorSoundaramourty, C
dc.creatorCorreia-de-Oliveira, A
dc.creatorDinis-Oliveira, R
dc.creatorOuaissi, A
dc.creatorCordeiro-da-Silva, A
dc.creatorSilvestre, R
dc.creatorEstaquier, J
dc.date.accessioned2019-01-08T09:55:06Z-
dc.date.available2019-01-08T09:55:06Z-
dc.date.issued2014
dc.identifier.issn1553-7366
dc.identifier.urihttps://repositorio-aberto.up.pt/handle/10216/118193-
dc.description.abstractLeishmania 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. © 2014 Rodrigues et al.
dc.description.sponsorshipThis work was supported by an ANR (Agence Nationale de la Recherche) grant (LeishApo) and the Seven Framework Programme (KINDReD) to JE. JE thanks the Canada Research Chair program for financial assistance. VR is supported by a doctoral fellowship from FCT (Fundação para a Ciência e Tecnologia); code SFRH/BD/64064/2009. RS is supported by Programa Ciência – financed by Programa Operacional Potencial Humano POPH – QREN– Tipologia 4.2 –Promocao do Emprego Cientıfico, co-funded by Fundo Social Europeu and National funding from Ministry of Science, Technology and Higher Education (MCTES). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.language.isoeng
dc.publisherPublic Library of Science
dc.relationinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F64064%2F2009/PT
dc.relation.ispartofPLoS Pathogens, vol.10(4): e1004096
dc.rightsopenAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.meshAnimals
dc.subject.meshFemale
dc.subject.meshGene Expression Regulation/immunology
dc.subject.meshGerminal Center/immunology
dc.subject.meshGerminal Center/parasitology
dc.subject.meshGerminal Center/pathology
dc.subject.meshImmunity, Humoral
dc.subject.meshInterleukin-10/immunology
dc.subject.meshLeishmania infantum/immunology
dc.subject.meshLeishmaniasis, Visceral/immunology
dc.subject.meshLeishmaniasis, Visceral/pathology
dc.subject.meshMacaca mulatta
dc.subject.meshMale
dc.subject.meshProto-Oncogene Proteins c-bcl-6/immunology
dc.subject.meshReceptors, CXCR5/immunology
dc.subject.meshSpleen/immunology
dc.subject.meshSpleen/parasitology
dc.subject.meshSpleen/pathology
dc.subject.meshTh1 Cells/immunology
dc.subject.meshTh1 Cells/pathology
dc.titleAbortive T Follicular Helper Development Is Associated with a Defective Humoral Response in Leishmania infantum-Infected Macaques
dc.typeArtigo em Revista Científica Internacional
dc.contributor.uportoInstituto de Investigação e Inovação em Saúde
dc.identifier.doi10.1371/journal.ppat.1004096
dc.relation.publisherversionhttps://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004096
Appears in Collections:I3S - Artigo em Revista Científica Internacional

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