Sinagapore-based researchers have uncovered a surprising mechanism showing how mosquito saliva can alter the human body’s immune response during chikungunya virus (CHIKV) infection, contributing to the country’s broader efforts to strengthen infectious disease preparedness.
The research carried out at the A*STAR Infectious Diseases Labs (A*STAR IDL) and published in Nature Communications, reveals that sialokinin, a bioactive peptide in Aedes mosquito saliva, binds to neurokinin receptors on immune cells and suppresses monocyte activation, thereby reducing inflammation and facilitating early viral dissemination. These findings offer new insight into how mosquito bites shape disease outcomes.
CHIKV is transmitted by Aedes mosquitoes (Aedes aegypti pictured) and causes painful joint swelling that can persist for months. As global temperatures rise, mosquito populations are expanding, heightening the risk of CHIKV and other mosquito-borne diseases in tropical regions such as Singapore.
The A*STAR team identified sialokinin, a protein in mosquito saliva, as a key factor that shapes how the body responds to infection. The study found that sialokinin binds to neurokinin receptors in the immune system, temporarily suppressing inflammation in the early stages of infection. Laboratory and pre-clinical studies revealed that this early dampening of the immune response allows the virus to spread more easily to other tissues, which may in turn contribute to severe symptoms later on.
Consistent with this, patients with more severe chikungunya symptoms were found to have higher levels of antibodies against sialokinin, indicating a stronger immune reaction to the peptide, which may contribute to disease severity.
“This study provides compelling evidence that mosquito salivary proteins are not just passive carriers of viruses but active modulators of host immunity,” said Dr Siew-Wai Fong, corresponding author and Senior Scientist at A*STAR IDL. “Targeting sialokinin or its receptor interactions could represent a novel therapeutic strategy to mitigate inflammation and improve outcomes in CHIKV and potentially other arboviral infections.”
While this research focused specifically on CHIKV, further investigations will be needed to understand whether similar immune mechanisms occur in other mosquito-borne infections such as dengue or Zika.
The findings underscore the importance of understanding vector-host interactions in the context of emerging infectious diseases. As climate change accelerates the spread of mosquito-borne viruses, identifying and neutralising salivary factors like sialokinin may offer new avenues for disease control and prevention. These insights not only enhance our preparedness for future outbreaks but also lay the groundwork for the development of targeted therapeutics and treatment strategies, ultimately strengthening public health responses to mosquito-borne threats.
The study also sheds light on the complex interaction between mosquito saliva and the human immune system. While the saliva can temporarily dampen inflammation in the early stages of infection, this effect helps the virus spread more easily before the immune system mounts a full response.
By bridging immunology, virology, and vector biology, the study opens new pathways to develop strategies for managing mosquito-borne diseases, improving therapeutics, and strengthening global health resilience in an era of climate-driven disease emergence.
Building on these discoveries, the A*STAR IDL team will continue exploring how modulating the effects of mosquito saliva proteins might help manage inflammation and infection. This work supports ongoing national efforts to use science and innovation to strengthen Singapore’s preparedness against emerging infectious diseases.
- Fong SW, Tan JJL, Sridhar V, et al. Mosquito salivary sialokinin reduces monocyte activation and chikungunya virus-induced inflammation via neurokinin receptors. Nat Commun. 2025;16(1):8644. doi:10.1038/s41467-025-64468-x