TY - JOUR
T1 - IL-17A-producing γδ T cells suppress early control of parasite growth by monocytes in the liver
AU - Sheel, Meru
AU - Beattie, Lynette
AU - Frame, Teija C.M.
AU - De Labastida Rivera, Fabian
AU - Faleiro, Rebecca J.
AU - Bunn, Patrick T.
AU - De Oca, Marcela Montes
AU - Edwards, Chelsea L.
AU - Ng, Susanna S.
AU - Kumar, Rajiv
AU - Amante, Fiona H.
AU - Best, Shannon E.
AU - McColl, Shaun R.
AU - Varelias, Antiopi
AU - Kuns, Rachel D.
AU - MacDonald, Kelli P.A.
AU - Smyth, Mark J.
AU - Haque, Ashraful
AU - Hill, Geoff R.
AU - Engwerda, Christian R.
N1 - Publisher Copyright:
© 2015 The Authors.
PY - 2015/12/15
Y1 - 2015/12/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84958259945&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1501046
DO - 10.4049/jimmunol.1501046
M3 - Article
SN - 0022-1767
VL - 195
SP - 5707
EP - 5717
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -