Mosquito Salivary Sialokinin Suppresses Monocyte Activation and Dampens Chikungunya-Induced Inflammation Through a Neurokinin Receptor-Associated Pathway

Abstract

Mosquito-borne chikungunya virus (CHIKV) continues to raise global concern as the disease can be highly debilitating and is spreading further across the globe. Mosquito bites have been shown to enhance arbovirus infection due to the activities of proteins in mosquito saliva. Mosquito salivary sialokinin, in particular, has been reported to promote vascular leakage to help viruses spread. Understanding how this protein affects CHIKV pathogenesis could help establish therapeutic strategies against the disease.  Here, we report that sialokinin restricted the activation of human myeloid cells, while antagonising neurokinin receptors abolished this effect. Importantly, sialokinin therapy effectively reduced inflammation and inhibited monocyte activation during CHIKV infection, demonstrated by decreased swelling of the footpads in virus-infected mice. Our findings point to a major role for sialokinin in regulating monocyte activation and affecting host immunity during CHIKV infection. Modulating sialokinin activities may offer new approaches for host-directed therapies against chikungunya.

Note:
Funding Information: The work was supported by the Ministry of Education, Singapore (MOE2015- T3-1-003), core research grants provided to A*STAR ID Labs by the Biomedical Research Council (BMRC) from the Agency for Science, Technology and Research (A*STAR), and a Career Development Fund (C210812043) awarded to SWF by A*STAR. The SIgN Multiplex Analysis of Proteins (MAP) platform was supported by a grant from the National Research Foundation, Immunomonitoring Service Platform (ISP) (NRF2017_SISFP09) from the National Research Foundation Singapore (NRF). SWF was supported by MOE AcRF Tier 3 grant (MOE2015-T3-1-003) from 2016 to 2020.

Conflict of Interests: All authors declare no conflicts of interest.

Informed Consent Statement: Human blood apheresis cones were obtained from healthy adult donors with written consent in accordance with guidelines from the Health Sciences Authority of Singapore (Reference No: 2017/2512).

Keywords: mosquito saliva, sialokinin, neurokinin receptors, joint inflammation, alphavirus infection, chikungunya virus, CHIKV, neglected tropical diseases