title: IL-17A-Producing γδ T Cells Suppress Early Control of Parasite Growth by Monocytes in the Liver.
abstract: Intracellular infections, such as those caused by the protozoan parasite Leishmania donovani, a causative agent of visceral leishmaniasis (VL), require a potent host proinflammatory response for control. IL-17 has emerged as an important proinflammatory cytokine required for limiting growth of both extracellular and intracellular pathogens. However, there are conflicting reports on the exact roles for IL-17 during parasitic infections and limited knowledge about cellular sources and the immune pathways it modulates. We examined the role of IL-17 in an experimental model of VL caused by infection of C57BL/6 mice with L. donovani and identified an early suppressive role for IL-17 in the liver that limited control of parasite growth. IL-17-producing γδ T cells recruited to the liver in the first week of infection were the critical source of IL-17 in this model, and CCR2(+) inflammatory monocytes were an important target for the suppressive effects of IL-17. Improved parasite control was independent of NO generation, but associated with maintenance of superoxide dismutase mRNA expression in the absence of IL-17 in the liver. Thus, we have identified a novel inhibitory function for IL-17 in parasitic infection, and our results demonstrate important interactions among γδ T cells, monocytes, and infected macrophages in the liver that can determine the outcome of parasitic infection.
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia;
authors.forename: Meru
authors.initials: M
authors.lastname: Sheel
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia;
authors.forename: Lynette
authors.initials: L
authors.lastname: Beattie
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia; School of Biomedical Sciences, University of Queensland, Brisbane, Queensland 4072, Australia;
authors.forename: Teija C M
authors.initials: TC
authors.lastname: Frame
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia;
authors.forename: Fabian
authors.initials: F
authors.lastname: de Labastida Rivera
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia; Queensland University of Technology, Institute of Health and Biomedical Innovation, Brisbane, Queensland 4059, Australia;
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Faleiro
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia; Institute of Glycomics, Griffith University, Gold Coast, Queensland 4215, Australia;
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Bunn
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia; School of Medicine, University of Queensland, Brisbane, Queensland 4072, Australia;
authors.forename: Marcela
authors.initials: M
authors.lastname: Montes de Oca
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia; School of Medicine, University of Queensland, Brisbane, Queensland 4072, Australia;
authors.forename: Chelsea L
authors.initials: CL
authors.lastname: Edwards
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia; School of Natural Sciences, Griffith University, Nathan, Queensland 4111, Australia;
authors.forename: Susanna S
authors.initials: SS
authors.lastname: Ng
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia; Netaji Subhas Institute of Technology, New Delhi 110078, India; and.
authors.forename: Rajiv
authors.identifier: http://orcid.org/0000-0003-2338-1494
authors.initials: R
authors.lastname: Kumar
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia;
authors.forename: Fiona H
authors.identifier: http://orcid.org/0000-0002-7788-5885
authors.initials: FH
authors.lastname: Amante
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia;
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Best
authors.affiliation: Centre for Molecular Pathology, University of Adelaide, Adelaide, South Australia 5005, Australia.
authors.forename: Shaun R
authors.initials: SR
authors.lastname: McColl
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia;
authors.forename: Antiopi
authors.initials: A
authors.lastname: Varelias
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia;
authors.forename: Rachel D
authors.initials: RD
authors.lastname: Kuns
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia;
authors.forename: Kelli P A
authors.initials: KP
authors.lastname: MacDonald
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia;
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia;
authors.forename: Ashraful
authors.initials: A
authors.lastname: Haque
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia;
authors.forename: Geoff R
authors.initials: GR
authors.lastname: Hill
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia; Christian.Engwerda@qimrberghofer.edu.au.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Engwerda
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007165:Immunosuppression Therapy; D020381:Interleukin-17 / Q000378:metabolism*; D007893:Leishmania donovani / Q000254:growth & development / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008099:Liver / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000469:parasitology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D054390:Receptors, CCR2 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000469:parasitology
chemical_list: C515335:Ccr2 protein, mouse; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054390:Receptors, CCR2; D013482:Superoxide Dismutase