Authors:
Sheel M, Beattie L, Frame TCM, De Labastida Rivera F, Faleiro RJ, Bunn PT, et al.
Authors notes:
J Immunol. 2015;195(12):5707-17.
Keywords:
Leishmania donovani, IL-17, IL-17A–Producing, inflammatory monocytes, Intracellular infections
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.