IL-17A-producing γδ T cells suppress early control of parasite growth by monocytes in the liver

Meru Sheel, Lynette Beattie, Teija C.M. Frame, Fabian De Labastida Rivera, Rebecca J. Faleiro, Patrick T. Bunn, Marcela Montes De Oca, Chelsea L. Edwards, Susanna S. Ng, Rajiv Kumar, Fiona H. Amante, Shannon E. Best, Shaun R. McColl, Antiopi Varelias, Rachel D. Kuns, Kelli P.A. MacDonald, Mark J. Smyth, Ashraful Haque, Geoff R. Hill, Christian R. Engwerda*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5707-5717
Number of pages11
JournalJournal of Immunology
Volume195
Issue number12
DOIs
Publication statusPublished - 15 Dec 2015
Externally publishedYes

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