title: IL-17A promotes susceptibility during experimental visceral leishmaniasis caused by Leishmania donovani.
abstract: 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 (Th)1 and Th2 responses. Immunity against this parasite is dependent on IFN-γ production and subsequent macrophage activation, and the Th2 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 Th17 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.
authors.affiliation: *Department of Pathology, Department of Veterinary Biosciences, and Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA cterrazas.05@gmail.com abhay.satoskar@osumc.edu.
authors.forename: Cesar
authors.initials: C
authors.lastname: Terrazas
authors.affiliation: *Department of Pathology, Department of Veterinary Biosciences, and Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Varikuti
authors.affiliation: *Department of Pathology, Department of Veterinary Biosciences, and Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kimble
authors.affiliation: *Department of Pathology, Department of Veterinary Biosciences, and Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Moretti
authors.affiliation: *Department of Pathology, Department of Veterinary Biosciences, and Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Prosper N
authors.initials: PN
authors.lastname: Boyaka
authors.affiliation: *Department of Pathology, Department of Veterinary Biosciences, and Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA cterrazas.05@gmail.com abhay.satoskar@osumc.edu.
authors.forename: Abhay R
authors.initials: AR
authors.lastname: Satoskar
mesh_terms: D000818:Animals; D004198:Disease Susceptibility; D006099:Granuloma / Q000276:immunology / Q000469:parasitology; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology*; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000469:parasitology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000469:parasitology; D009504:Neutrophils / Q000276:immunology / Q000469:parasitology; D053722:Receptors, Interleukin-17 / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000469:parasitology; D018418:Th2 Cells / Q000276:immunology / Q000469:parasitology
chemical_list: D020381:Interleukin-17; D053722:Receptors, Interleukin-17; D007371:Interferon-gamma
keywords: Th17; granuloma; monocytes; neutrophils; γδ T cells