Selective TLR ligand stimulation enhances in vivo mosquito-borne flavivirus pathogenicity
Issued Date
2025-09-23
Resource Type
ISSN
26391856
eISSN
22111247
Scopus ID
2-s2.0-105014527845
Journal Title
Cell Reports
Volume
44
Issue
9
Rights Holder(s)
SCOPUS
Bibliographic Citation
Cell Reports Vol.44 No.9 (2025)
Suggested Citation
Suzuki T., Miyata Y., Haga S., Itoh Y., Tanaka T., Hishinuma T., Orba Y., Eshita Y., Sakai Y., Kurosu T., Tajima S., Lim C.K., Saijo M., Yamanaka A., Phanitchat T., Morales Vargas R.E., Okuzaki D., Sawa H., Satoh T., Akira S., Matsuura Y., Okamoto T. Selective TLR ligand stimulation enhances in vivo mosquito-borne flavivirus pathogenicity. Cell Reports Vol.44 No.9 (2025). doi:10.1016/j.celrep.2025.116210 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/111949
Title
Selective TLR ligand stimulation enhances in vivo mosquito-borne flavivirus pathogenicity
Author's Affiliation
The University of Osaka
Institute of Science Tokyo
Hokkaido University
National Institute of Infectious Diseases
Juntendo University School of Medicine
Faculty of Science, Mahidol University
Research Institute for Microbial Diseases
Faculty of Tropical Medicine, Mahidol University
WPI Immunology Frontier Research Center, The University of Osaka
Institute of Science Tokyo
Hokkaido University
National Institute of Infectious Diseases
Juntendo University School of Medicine
Faculty of Science, Mahidol University
Research Institute for Microbial Diseases
Faculty of Tropical Medicine, Mahidol University
WPI Immunology Frontier Research Center, The University of Osaka
Corresponding Author(s)
Other Contributor(s)
Abstract
Mosquito saliva facilitates pathogen transmission and enhances the severity of diseases caused by mosquito-borne viruses; however, the underlying mechanisms are unknown. Here, we demonstrate that mosquito salivary gland extracts (SGEs) enhance flaviviral pathogenicity in vivo by activating innate immune responses following the accumulation of immune cells at the infection site. Among the innate immune signaling pathways, the TLR2 pathway enhances flaviviral pathogenicity in a manner similar to that of SGEs. TLR2 ligands and SGEs induce neutrophils to secrete chemokines that recruit virus-permissive monocytes and macrophages to infection sites. SGEs activate TLR2, and inhibition of TLR2 signaling markedly reduces mosquito-saliva-enhanced viral pathogenicity. Overall, this study provides important insights into vector-host interactions and suggests that TLR2 is a potential target for preventing mosquito-borne flaviviral infection.