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

PLoS Pathogens

Laure Campillo-Gimenez¹  Ana Correia-de-Oliveira¹  Calaiselvy Soundaramourty¹  Vasco Rodrigues¹  Jérôme Estaquier²  Ricardo Jorge Dinis-Oliveira³  Anabela Cordeiro-da-Silva³  Ricardo Silvestre⁴  Ali Ouaissi⁴  Mireille Laforge⁵ 

[1] CNRS FR3636, Université Paris Descartes, Paris, France;Departamento de Medicina Legal e Ciências Forenses, Faculdade de Medicina, Universidade do Porto, Porto, Portugal;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;Parasite Disease Group, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal

关键词: Parasitic diseases;    T helper cells;    B cells;    Macaque;    Cell differentiation;    Rhesus monkeys;    Spleen;    Lymph nodes;   

DOI  :  10.1371/journal.ppat.1004096

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY