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Differences in innate IFNγ and IL-17 responses to Bordetella pertussis between BALB/c and C57BL/6 mice: role of γδT cells, NK cells, and dendritic cells

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Abstract

Cell-mediated immune responses characterized by the secretion of IFNγ and IL-17 play an important role in the immune response to Bordetella pertussis (B. pertussis). We investigated innate sources of IFNγ and IL-17 upon stimulation of spleen cells from BALB/c (B/c) and C57BL/6 (B6) mice with heat-killed B. pertussis (hkBp). Spleen cells from B/c mice secreted less IFNγ and more IL-17 than those from B6 mice. Innate IFNγ was produced predominantly by NK cells in B/c mice and by CD8 T cells and NK cells in B6 mice. Innate IL-17 was produced primarily by γδT cells in both mouse strains. The secretion of IFNγ was abrogated by anti-IL-12, and the production of IL-17 was abolished by anti-IL-1β- and anti-IL23-neutralizing antibodies. B/c dendritic cells (DCs) stimulated with hkBp secreted significantly more IL-1β and less IL-12 than B6 DCs. Differences in JNK phosphorylation in DCs suggest that this pathway plays a role in the differences between B/c and B6 strains. Mixed cultures of DCs and γδT cells from B/c and B6 showed that cytokines from DCs as well as γδT cell-intrinsic factors contributed to the robust innate IL-17 response in B/c strain. Stimulation of γδT cells with IL-1β and IL-23 was sufficient for IL-17 secretion whereas IL-12 inhibited the secretion of IL-17. A larger fraction of γδT cells were γδT-17 cells in B/c mice than B6 mice. Our data indicate important roles for genetically determined factors in the innate IFNγ and IL-17 responses to B. pertussis.

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Acknowledgements

This work was supported by generous gifts from the BMWLR and the John and Winifred Hayward Foundations. We thank Dr. Tod Merkel (Rockville, MD) for the D420 strain of Bordetella pertussis.

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  1. Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, 725 Harrison St, West Lafayette, IN, 47907, USA

    Yung-Yi C. Mosley, Fangjia Lu & Harm HogenEsch

  2. Purdue Institute of Inflammation, Immunology and Infectious Diseases, Purdue University, West Lafayette, IN, 47907, USA

    Harm HogenEsch

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  1. Yung-Yi C. Mosley
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Correspondence to Harm HogenEsch.

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The experimental animal studies were performed in strict accordance with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Purdue University Animal Care and Use Committee.

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Mosley, YY.C., Lu, F. & HogenEsch, H. Differences in innate IFNγ and IL-17 responses to Bordetella pertussis between BALB/c and C57BL/6 mice: role of γδT cells, NK cells, and dendritic cells. Immunol Res 65, 1139–1149 (2017). https://doi.org/10.1007/s12026-017-8957-4

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