title: Interleukin 17A acts synergistically with interferon γ to promote protection against Leishmania infantum infection.
abstract: Interleukin 17 (IL-17) is an inflammatory cytokine that plays a protective role against intracellular parasites. The role of IL-17 during Leishmania infection remains controversial and poorly defined. We evaluated whether IL-17 participates in the host immune response to Leishmania infantum. IL-17A is present in sera from patients with visceral leishmaniasis and decreases after successful treatment. In C57BL/6 infected mice, higher production of IL-17A coincided with the peak of parasitism. Il17ra(-/-) mice were more susceptible to infection and also exhibited reduced inflammatory infiltration and interferon γ (IFN-γ)-expressing CD4+ T-cell frequencies than wild-type mice. The frequencies of FoxP3+ CD4+ T cells and interleukin 10 (IL-10)-expressing CD4+ T cells were increased in Il17ra(-/-) mice. We also demonstrated that IL-17A acts synergistically with IFN-γ to potentiate NO production and leishmanicidal activity in infected macrophages. Therefore, our results indicate that L. infantum induces IL-17A production, which promotes the control of parasite replication by strengthening T-helper type 1 responses and NO production and prevents regulatory T-cell and IL-10-expressing T-cell expansion.
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo.
authors.forename: Manuela Sales Lima
authors.initials: MS
authors.lastname: Nascimento
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Carregaro
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo.
authors.forename: Djalma Souza
authors.initials: DS
authors.lastname: Lima-Júnior
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo.
authors.forename: Diego Luís
authors.initials: DL
authors.lastname: Costa
authors.affiliation: Molecular Immunology and Embryology UMR6218, University of Orleans and CNRS, Orleans, France.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington.
authors.forename: Malcolm S
authors.initials: MS
authors.lastname: Duthie
authors.affiliation: Center for Biology and Health Sciences, Federal University of Sergipe, Aracaju, Brazil.
authors.forename: Amélia
authors.initials: A
authors.lastname: de Jesus
authors.affiliation: Center for Biology and Health Sciences, Federal University of Sergipe, Aracaju, Brazil.
authors.forename: Roque Pacheco
authors.initials: RP
authors.lastname: de Almeida
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo.
authors.forename: João Santana
authors.initials: JS
authors.lastname: da Silva
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000502:physiology*; D020381:Interleukin-17 / Q000502:physiology*; D018314:Leishmania infantum / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000097:blood / Q000276:immunology* / Q000469:parasitology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D055815:Young Adult
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D007371:Interferon-gamma
keywords: IL-17; Leishmania infantum; nitric oxide; visceral leishmaniasis