Abortive T Follicular Helper Development Is Associated with a Defective Humoral Response in Leishmania infantum-Infected Macaques
| Autor: | Ali Ouaissi, Ana Correia-de-Oliveira, Ricardo Jorge Dinis-Oliveira, Laure Campillo-Gimenez, Calaiselvy Soundaramourty, Jérôme Estaquier, Mireille Laforge, Ricardo Silvestre, Vasco Rodrigues, Anabela Cordeiro-da-Silva |
|---|---|
| Přispěvatelé: | Instituto de Investigação e Inovação em Saúde, CNRS FR3636, Faculty of Medecine des Saint-Pères, Paris Descartes University , Paris , France. |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
B Cells [SDV]Life Sciences [q-bio] Spleen/parasitology Receptors CXCR5/immunology Protozoology Germinal Center/pathology Biochemistry Th1 Cells/pathology White Blood Cells 0302 clinical medicine Animal Cells Lymphoid Organs Leishmania infantum Memory B cell lcsh:QH301-705.5 ComputingMilieux_MISCELLANEOUS Protozoans Leishmania 0303 health sciences education.field_of_study Immune System Proteins T Cells Spleen/pathology 3. Good health Interleukin-10 medicine.anatomical_structure Proto-Oncogene Proteins c-bcl-6 Leishmaniasis Visceral Cytokines Female Anatomy Cellular Types Research Article lcsh:Immunologic diseases. Allergy Receptors CXCR5 Spleen/immunology Immune Cells Population Immunology Leishmaniasis Visceral/pathology Spleen Immunopathology Biology Microbiology Antibodies Lymphatic System Immune Activation 03 medical and health sciences Immune system Germinal Center/immunology Virology Genetics medicine Animals Proto-Oncogene Proteins c-bcl-6/immunology Th1 Cells/immunology education Antibody-Producing Cells Molecular Biology B cell 030304 developmental biology Blood Cells Gene Expression Regulation/immunology Leishmania infantum/immunology Germinal Center/parasitology Organisms Immunity Germinal center Biology and Life Sciences Proteins Cell Biology Th1 Cells Molecular Development biology.organism_classification Germinal Center Macaca mulatta Parasitic Protozoans Acquired Immune System Immunity Humoral Leishmaniasis Visceral/immunology Chronic infection lcsh:Biology (General) Gene Expression Regulation Immune System Humoral Immunity Parasitology Clinical Immunology lcsh:RC581-607 Interleukin-10/immunology 030215 immunology Developmental Biology |
| Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP PLoS Pathogens PLoS Pathogens, Public Library of Science, 2014, 10 (4), pp.e1004096. ⟨10.1371/journal.ppat.1004096⟩ PLoS Pathogens, Vol 10, Iss 4, p e1004096 (2014) |
| ISSN: | 1553-7366 1553-7374 |
| DOI: | 10.1371/journal.ppat.1004096⟩ |
| Popis: | 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. Author Summary We introduced a non-human primate model for visceral leishmaniasis by intravenous injection of L. infantum promastigotes in rhesus macaques and followed the animals for a period of eight months. In this model, parasites dock to the liver and spleen shortly after inoculation and remain in these visceral compartments during all the acute phase of infection. However, at the chronic phase, additional body locations appeared colonized (lymph nodes, bone marrow). During the acute phase, a Th1-polarized CD4 T cell response develops in the spleen, but, and concomitant with parasite growth, it waned at the chronic phase. Furthermore, we observed the acute expansion of a splenic T follicular helper (Tfh) cell population, a CD4+ T cell subset specialized to assist B cells in the production of antigen-specific antibody. These cells were localized in close association with B cell follicles but, interestingly, the Tfh population is lost at the chronic phase. Nevertheless, there was a close association between the development of Tfh cells and the differentiation of B cells that produce L. infantum-specific IgG. Thus, our results suggest that Tfh cells are important in instructing B cells to produce parasite-specific antibodies during VL, but their abortive differentiation precludes the continuous production of specific-IgG. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|