title: A Leishmania infantum cytosolic tryparedoxin activates B cells to secrete interleukin-10 and specific immunoglobulin.
abstract: The immune evasion mechanisms of pathogenic trypanosomatids involve a multitude of phenomena such as the polyclonal activation of lymphocytes, cytokine modulation and the enhanced detoxification of oxygen reactive species. A trypanothione cascade seems to be involved in the detoxification process. It was recently described and characterized a tryparedoxin (LiTXN1) involved in Leishmania infantum cytoplasmatic hydroperoxide metabolism. LiTXN1 is a secreted protein that is up-regulated in the infectious form of the parasite, suggesting that it may play an important role during infection. In the present study, we investigated whether recombinant LiTXN1 (rLiTXN1) affects T- and B-cell functions in a murine model. We observed a significant increase in the CD69 surface marker on the B-cell population in total spleen cells and on isolated B cells from BALB/c mice after in vitro rLiTXN1 stimulus. Activated B-cells underwent further proliferation, as indicated by increased [(3)H]thymidine incorporation. Cytokine quantification showed a dose-dependent up-regulation of interleukin (IL)-10 secretion. B cells were identified as a source of this secretion. Furthermore, intraperitoneal injection of rLiTXN1 into BALB/c mice triggered the production of elevated levels of rLiTXN1-specific antibodies, predominantly of the immunoglobulin M (IgM), IgG1 and IgG3 isotypes, with a minimum reactivity against other heterologous antigens. Taken together, our data suggest that rLiTXN1 may participate in immunopathological processes by targeting B-cell effector functions, leading to IL-10 secretion and production of specific antibodies.
authors.affiliation: Departamento de Bioquímica, Faculdade de Farmácia and Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Sofia Menezes
authors.initials: SM
authors.lastname: Cabral
authors.forename: Ricardo Leal
authors.initials: RL
authors.lastname: Silvestre
authors.forename: Nuno Moreira
authors.initials: NM
authors.lastname: Santarém
authors.forename: Joana Costa
authors.initials: JC
authors.lastname: Tavares
authors.forename: Ana Franco
authors.initials: AF
authors.lastname: Silva
authors.forename: Anabela
authors.initials: A
authors.lastname: Cordeiro-da-Silva
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003600:Cytosol / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D007074:Immunoglobulin G / Q000096:biosynthesis; D016753:Interleukin-10 / Q000378:metabolism*; D037181:Lectins, C-Type; D018314:Leishmania infantum / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013154:Spleen / Q000276:immunology; D013879:Thioredoxins / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology; D000099192:CD69 Antigens
chemical_list: D000913:Antibodies, Protozoan; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D007074:Immunoglobulin G; D016753:Interleukin-10; D037181:Lectins, C-Type; D013879:Thioredoxins; D000099192:CD69 Antigens; C114110:tryparedoxin