Interleukin-17A Promotes CD8⁺ T Cell Cytotoxicity To Facilitate West Nile Virus Clearance

Authors

Dhiraj Acharya, University of Southern MississippiFollow
Penghua Wang, Yale University School of MedicineFollow
Amber M. Paul, University of Southern MississippiFollow
Jianfeng Dai, Yale University School of MedicineFollow
David Gate, Zilkha Neurogenetic InstituteFollow
Jordan E. Lowery, University of Southern Mississippi
Dobrivoje S. Stokic, Center for Neuroscience and Neurological Recovery, Methodist Rehabilitation Center, Jackson, MississippiFollow
A. Arturo Leis, Center for Neuroscience and Neurological Recovery, Methodist Rehabilitation Center, Jackson, MississippiFollow
Richard A. Flavell, Yale University School of MedicineFollow
Terrence Town, Zilkha Neurogenetic InstituteFollow
Erol Fikrig, Yale University School of MedicineFollow
Fengwei Bai, University of Southern MississippiFollow

Document Type

Article

Publication Date

1-1-2017

Department

Biological Sciences

School

Biological, Environmental, and Earth Sciences

Abstract

CD8⁺ T cells are crucial components of immunity and play a vital role in recovery from West Nile virus (WNV) infection. Here, we identify a previously unrecognized function of interleukin-17A (IL-17A) in inducing cytotoxic-mediator gene expression and promoting CD8⁺ T cell cytotoxicity against WNV infection in mice. We find that IL-17A-deficient (Il17a^−/−) mice are more susceptible to WNV infection and develop a higher viral burden than wild-type (WT) mice. Interestingly, the CD8⁺ T cells isolated from Il17a^−/− mice are less cytotoxic and express lower levels of cytotoxic-mediator genes, which can be restored by supplying recombinant IL-17A in vitro and in vivo. Importantly, treatment of WNV-infected mice with recombinant IL-17A, as late as day 6 postinfection, significantly reduces the viral burden and increases survival, suggesting a therapeutic potential for IL-17A. In conclusion, we report a novel function of IL-17A in promoting CD8⁺ T cell cytotoxicity, which may have broad implications in other microbial infections and cancers.

Publication Title

Journal of Virology

Volume

91

Issue

1

First Page

1

Last Page

22

Recommended Citation

Acharya, D., Wang, P., Paul, A. M., Dai, J., Gate, D., Lowery, J. E., Stokic, D. S., Leis, A., Flavell, R. A., Town, T., Fikrig, E., Bai, F. (2017). Interleukin-17A Promotes CD8⁺ T Cell Cytotoxicity To Facilitate West Nile Virus Clearance. Journal of Virology, 91(1), 1-22.
Available at: https://aquila.usm.edu/fac_pubs/16498