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

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.