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 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.
CNRS FR3636, Université Paris Descartes, Paris, France; Parasite Disease Group, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
Vasco
V
Rodrigues
CNRS FR3636, Université Paris Descartes, Paris, France.
Mireille
M
Laforge
CNRS FR3636, Université Paris Descartes, Paris, France.
Laure
L
Campillo-Gimenez
CNRS FR3636, Université Paris Descartes, Paris, France.
Calaiselvy
C
Soundaramourty
Department of Sciences, Advanced Institute of Health Sciences - North (ISCS-N), CESPU, CRL, Gandra, Portugal; Molecular Oncology GRP and Virology LB, Instituto Português de Oncologia-Porto, Porto, Portugal.
Ana
A
Correia-de-Oliveira
Department of Sciences, Advanced Institute of Health Sciences - North (ISCS-N), CESPU, CRL, Gandra, Portugal; Molecular Oncology GRP and Virology LB, Instituto Português de Oncologia-Porto, Porto, Portugal; Departamento de Medicina Legal e Ciências Forenses, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
Ricardo Jorge
RJ
Dinis-Oliveira
Parasite Disease Group, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
Ali
A
Ouaissi
Parasite Disease Group, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal; Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
Anabela
A
Cordeiro-da-Silva
Parasite Disease Group, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
Ricardo
R
Silvestre
CNRS FR3636, Université Paris Descartes, Paris, France; Université Laval, Centre de Recherche en Infectiologie, Québec, Canada.
Jérôme
J
Estaquier
D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D018858:Germinal Center / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D056724:Immunity, Humoral; D016753:Interleukin-10 / Q000276:immunology; D018314:Leishmania infantum / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000473:pathology; D008253:Macaca mulatta; D008297:Male; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000276:immunology; D054380:Receptors, CXCR5 / Q000276:immunology; D013154:Spleen / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology
D051560:Proto-Oncogene Proteins c-bcl-6; D054380:Receptors, CXCR5; D016753:Interleukin-10