Abstract
The role of IL-17A is important in protection against lung infection with Chlamydiae, an obligate intracellular bacterial pathogen. In this study, we explored the producers of IL-17A in chlamydial lung infection and specifically tested the role of major IL-17A producers in protective immunity. We found that γδT cells and Th17 cells are the major producers of IL-17A at the early and later stages of chlamydial infection, respectively. Depletion of γδT cells in vivo at the early postinfection (p.i.) stage, when most γδT cells produce IL-17A, failed to alter Th1 responses and bacterial clearance. In contrast, the blockade of IL-17A at the time when IL-17A was mainly produced by Th17 (day 7 p.i.) markedly reduced the Th1 response and increased chlamydial growth. The data suggest that the γδ T cell is the highest producer of IL-17A in the very early stages of infection, but the protection conferred by IL-17A is mainly mediated by Th17 cells. In addition, we found that depletion of γδ T cells reduced IL-1α production by dendritic cells, which was associated with a reduced Th17 response. This finding is helpful to understand the variable role of IL-17A in different infections and to develop preventive and therapeutic approaches against infectious diseases by targeting IL-17A.
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Acknowledgements
This work was supported by grants (to XY) from the Canadian Institutes of Health Research (CIHR), the Manitoba Health Research Council (MHRC) and the Manitoba Institute of Child Health (MICH) and grants (to HB) from the National Natural Science Foundation of China (31070797), the Key Program: 15JCZDJC34900 and 11JCZDJC16200 from Tianjin Municipal Science and Technology Commission (TSTC). XG was a trainee in CIHR National Training Program in Allergy/asthma and a holder of an MICH Studentship. AGJ was a trainee in the CIHR/International Centre for Infectious Diseases (ICID) National Training Program in Infectious Diseases and a holder of an MHRC postdoctoral fellowship. XY was the Canada Research Chair in Infection and Immunity.
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Bai, H., Gao, X., Zhao, L. et al. Respective IL-17A production by γδ T and Th17 cells and its implication in host defense against chlamydial lung infection. Cell Mol Immunol 14, 850–861 (2017). https://doi.org/10.1038/cmi.2016.53
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DOI: https://doi.org/10.1038/cmi.2016.53
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