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IL‐17A promotes susceptibility during experimental visceral leishmaniasis caused by Leishmania donovani
Author(s) -
Terrazas Cesar,
Varikuti Sanjay,
Kimble Jennifer,
Moretti Ellen,
Boyaka Prosper N.,
Satoskar Abhay R.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.15-277202
Subject(s) - leishmania donovani , visceral leishmaniasis , immunology , immune system , interleukin 17 , spleen , leishmania , inflammation , biology , leishmaniasis , cytokine , intracellular parasite , interleukin 10 , macrophage , interferon gamma , parasite hosting , in vitro , biochemistry , world wide web , computer science
Leishmania donovani is an intracellular parasite that infects professional phagocytes and causes visceral leishmaniasis (VL). The immune response during VL has been extensively studied in the context of T‐helper (T h ) 1 and T h 2 responses. Immunity against this parasite is dependent on IFN‐γ production and subsequent macrophage activation, and the T h 2 response promotes granuloma formation. The cytokine IL‐17A is associated with neutrophilic inflammation. Depletion of neutrophils during experimental VL results in enhanced parasitic loads. Furthermore, although patients resistant to VL showed enhanced levels of IL‐17A in circulation, little is known about the role of IL‐17A during VL infection. Here, we used IL‐17A‐deficient mice and IL‐17A reporter mice to address the role of IL‐17A during VL. IL‐17A –/– mice were highly resistant to VL infection, showing decreased parasites in the liver and spleen. This unexpected phenotype was associated with enhanced IFN‐γ production by T cells and decreased accumulation of neutrophils and monocytes, resulting in reduced number of granulomas. We also found γδ T and T h 17 cells as the main IL‐17A + cells during VL infection. Our data reveal an unexpected role of IL‐17A rendering susceptibility against L. donovani by regulating the IFN‐γ response and promoting detrimental inflammation.—Terrazas, C., Varikuti, S., Kimble, J., Moretti, E., Boyaka, P. N., Satoskar, A. R., IL‐17A promotes susceptibility during experimental visceral leishmaniasis caused by Leishmania donovani . FASEB J. 30, 1135‐1143 (2016). www.fasebj.org