QIMR Berghofer

IL-17A-Producing gammadelta T Cells Suppress Early Control of Parasite Growth by Monocytes in the Liver


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 gammadelta 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 gammadelta T cells, monocytes, and infected macrophages in the liver that can determine the outcome of parasitic infection.

Authors Sheel, Meru; Beattie, L; Frame, Teija C. M.; Rivera, Fabian de Labastida; Faleiro, Rebecca; Bunn, Patrick T.; de Oca, Marcela Montes; Edwards, Chelsea L.; Ng, Susanna S.; Kumar, Rajiv; Amante, FH; Best, Shannon E.; McColl, Shaun R.; Varelias, Antiopi; Kuns, Rachel; MacDonald, Kelli P. A.; Smyth, Mark J.; Haque, Ashraful; Hill, Geoffrey R.; Engwerda, C
Pages 5707-17
Volume 195
Date 1/12/2015
Grant ID
Funding Body NHMRC
URL http://www.ncbi.nlm.nih.gov/pubmed/?term=10.4049/jimmunol.1501046
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