Interleukin 17A Acts Synergistically With Interferon gamma to Promote Protection Against Leishmania infantum Infection

Author(s)

Lima Nascimento, Manuela Sales ^[1] ; Carregaro, Vanessa ^[1] ; Lima-Junior, Djalma Souza ^[1] ; Costa, Diego Luis ^[1] ; Ryffel, Bernhard ^{[2, 3]} ; Duthie, Malcolm S. ^[4] ; de Jesus, Amelia ^[5] ; de Almeida, Roque Pacheco ^[5] ; da Silva, Joao Santana ^[1]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Aracaju - Brazil

^[2] CNRS, F-45071 Orleans - France

^[3] Univ Orleans, UMR6218, Orleans - France

^[4] Infect Dis Res Inst, Seattle, WA - USA

^[5] Univ Fed Sergipe, Ctr Biol & Hlth Sci, Aracaju - Brazil

• Document type: Journal article
• Source: Journal of Infectious Diseases; v. 211, n. 6, p. 1015-1026, MAR 15 2015.
• Web of Science Citations: 42

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 gamma Il17ra(-/-) mice were more susceptible to infection and also exhibited reduced inflammatory infiltration and interferon gamma (IFN-gamma)-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-gamma 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. (AU)

• FAPESP's process: 13/01967-2 - Characterization of the mechanisms involved in the generation and modulation of protective immune response during Leishmania infantum infection
• Grantee: Manuela Sales Lima Nascimento
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/14524-9 - Modulation of T lymphocytes differentiation in infections by Protozoa, Fungi and Bacteria
• Grantee: João Santana da Silva
• Support Opportunities: Research Projects - Thematic Grants