title: Leishmania (Viannia) braziliensis amastigotes induces the expression of TNFα and IL-10 by human peripheral blood mononuclear cells in vitro in a TLR4-dependent manner.
abstract: While the role of Toll-like receptors (TLRs) has been investigated in murine models of tegumentary leishmaniasis caused by Leishmania (Viannia) braziliensis, the interaction between TLRs and Leishmania sp. has not been investigated in human cells. The aim of this study was to evaluate the involvement of TLR4 in cytokine production of human peripheral blood mononuclear cells (PBMCs) induced by L. braziliensis, and whether the parasite alters the expression of TLR4 on monocytes/macrophages. Amastigote forms were obtained from mice lesions and PBMCs were isolated from healthy donors. PBMCs were cultured in absence or presence of IFNγ, TLR4 neutralizing antibodies, natural antagonist of TLR4 (Bartonella LPS), TLR4 agonist (E. coli LPS), and amastigote forms. The concentrations of tumor necrosis factor (TNFα) and interleukin 10 (IL-10) were assayed by ELISA and TLR4 expression by flow cytometry. Amastigotes forms of L. braziliensis induced TNFα and IL-10 production only in IFNγ-primed PBMCs. The TNFα and IL-10 production was inhibited by TLR4 neutralization, both with anti-TLR4 antibodies and Bartonella LPS. Interestingly, addition of E. coli LPS further increased TNFα but not IL-10 production induced by L. braziliensis amastigotes. Amastigotes of L. braziliensis strongly reduced membrane TLR4 expression on monocytes/macrophages, apparently by internalization after the infection. The present study reveals that TLR4 drives the production of TNFα and IL-10 induced by L. braziliensis amastigotes and that the parasites decrease TLR4 expression on monocyte surface.
authors.affiliation: Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Hélio
authors.initials: H
authors.lastname: Galdino
authors.affiliation: Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Saar Gomes
authors.affiliation: Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil; Department of Internal Medicine, Radboud University Medical Center and Radboud Center of Infectious Diseases (RCI), Nijmegen, The Netherlands.
authors.forename: Jessica Cristina
authors.initials: JC
authors.lastname: Dos Santos
authors.affiliation: Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Lívia Lara
authors.initials: LL
authors.lastname: Pessoni
authors.affiliation: Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Anetícia Eduarda
authors.initials: AE
authors.lastname: Maldaner
authors.affiliation: Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Stéfanne Madalena
authors.initials: SM
authors.lastname: Marques
authors.affiliation: Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Clayson Moura
authors.initials: CM
authors.lastname: Gomes
authors.affiliation: Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Miriam Leandro
authors.initials: ML
authors.lastname: Dorta
authors.affiliation: Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Milton Adriano Pelli
authors.initials: MA
authors.lastname: de Oliveira
authors.affiliation: Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil; Department of Internal Medicine, Radboud University Medical Center and Radboud Center of Infectious Diseases (RCI), Nijmegen, The Netherlands. Electronic address: leo.joosten@radboudumc.nl.
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.affiliation: Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil. Electronic address: fatimardias@gmail.com.
authors.forename: Fátima
authors.initials: F
authors.lastname: Ribeiro-Dias
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology*; D007892:Leishmania braziliensis / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: C508609:IL10 protein, human; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: Amastigotes; Human PBMCs; IL-10; Leishmania (Viannia) braziliensis; TLR4; TNFα