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

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Sheel, Meru
Beattie, Lynette
Frame, Teija CM
Rivera, Fabian de Labastida
Faleiro, Rebecca J
Bunn, Patrick T
de Oca, Marcela Montes
Edwards, Chelsea L
Ng, Susanna S
Kumar, Rajiv
Amante, Fiona H
Best, Shannon E
McColl, Shaun R
Varelias, Antiopi
Kuns, Rachel D
MacDonald, Kelli PA
Smyth, Mark J
Haque, Ashraful
Hill, Geoff R
Engwerda, Christian R
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2015
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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.

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Journal of Immunology
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195
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12
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Immunology
Immunology not elsewhere classified
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