Mosquito salivary sialokinin reduces monocyte activation and chikungunya virus-induced inflammation via neurokinin receptors

Mosquito salivary sialokinin reduces monocyte activation and chikungunya virus-induced inflammation via neurokinin receptors

Nature Communications

10.1038/s41467-025-64468-x

https://doi.org/10.1038/s41467-025-64468-x

Siew-Wai Fong, Jeslin J. L. Tan, Vaishnavi Sridhar, Siti Naqiah Amrun, Vanessa K. X. Neo, Nathan Wong, Bernett Lee, Yi-Hao Chan, Anthony Torres-Ruesta, Liang Hui. Loo, Anna X. Y. Loo, Sarah K. W. Tan, Rhonda S. L. Chee, Tze-Kwang Chua, Angeline Rouers, Guillaume Carissimo, Fok-Moon Lum, Yee-Sin Leo, Laurent Renia, R. Manjunatha Kini, Lisa F. P. Ng

20 October 2025

Fong, S.-W., Tan, J. J. L., Sridhar, V., Amrun, S. N., Neo, V. K. X., Wong, N., Lee, B., Chan, Y.-H., Torres-Ruesta, A., Loo, L. Hui., Loo, A. X. Y., Tan, S. K. W., Chee, R. S. L., Chua, T.-K., Rouers, A., Carissimo, G., Lum, F.-M., Leo, Y.-S., Renia, L., et al. (2025). Mosquito salivary sialokinin reduces monocyte activation and chikungunya virus-induced inflammation via neurokinin receptors. Nature Communications, 16(1). https://doi.org/10.1038/s41467-025-64468-x

Abstract Global warming is expanding mosquito habitats and increasing mosquito-borne diseases. In tropical and sub-tropical regions, chikungunya virus (CHIKV) transmitted by Aedes mosquitoes has become a major concern due to the debilitating chronic joint disease it causes. Mosquito saliva contains bioactive factors that enhance viral infection, with sialokinin identified as a key contributor to vascular leakage and viral spread in mice. Here, we demonstrate that sialokinin binds to neurokinin receptors and restricts the activation of human myeloid cells. Mechanistically, sialokinin facilitates early viral dissemination, as evidenced by increased viral load in the contralateral footpad at 1 day post-infection, and significantly reduces circulating CD169+ monocytes while suppressing IFN-γ-producing T-cell-driven inflammation, as reflected by reduced joint footpad swelling in female CHIKV-infected mice. Clinically, patients with severe CHIKV disease exhibited higher levels of IgG antibodies against sialokinin, which correlated with higher viral loads and systemic inflammatory markers. Our findings highlight the multifaceted role of sialokinin in facilitating early viral dissemination and modulating host immunity during CHIKV infection. Given the growing threat of mosquito-borne diseases in a warming, disease-burdened world, targeting mosquito salivary factors like sialokinin could offer a novel therapeutic strategy to mitigate viral-induced inflammation and improve clinical outcomes.

Attribution 4.0 International (CC BY 4.0)

This research / project is supported by the Ministry of Education, Singapore - MOE Academic Research Fund Tier 3
Grant Reference no. : MOE2015-T3-1-003

This research / project is supported by the National Medical Research Council - Open Fund Large Collaborative Grant
Grant Reference no. : OF-LCG19May-0034

This research / project is supported by the Biomedical Research Council (BMRC) from the Agency for Science, Technology and Research (A*STAR) - Career Development Fund
Grant Reference no. : C210812043)

This research is supported by core funding from: Biomedical Research Council (BMRC)
Grant Reference no. : A*STAR CRF

https://oar.a-star.edu.sg/communities-collections/articles/23234

2041-1723

A*STAR Infectious Disease Labs

https://doi.org/10.1038/s41467-025-64468-x