Vector-borne diseases are responsible for over a billion infections each year and nearly one million deaths. Mosquito-borne dengue virus, West Nile, Japanese encephalitis, Zika, Chikungunya, and Rift Valley Fever viruses constitute major public health problems in regions with high densities of arthropod vectors. During the initial step of the transmission cycle, vector, host, and virus converge at the bite site, where local immune cells interact with the vector's saliva. Hematophagous mosquito saliva is a mixture of bioactive components known to modulate vertebrate hemostasis, immunity, and inflammation during the insect's feeding process. The capacity of mosquito saliva to modulate the host immune response has been well-studied over the last few decades and has led to the consensus that the presence of saliva is linked to the enhancement of virus transmission, host susceptibility, disease progression, viremia levels, and mortality. We review some of the major aspects of the interactions between mosquito saliva and the host immune response that may be useful for future studies on the control of arboviruses.
Mosquito-borne viruses are a growing global threat. Initial viral inoculation occurs in the skin via the mosquito ‘bite’, eliciting immune responses that shape the establishment of infection and pathogenesis. Here we assess the cutaneous innate and adaptive immune responses to controlled Aedes aegypti feedings in humans living in Aedes-endemic areas. In this single-arm, cross-sectional interventional study (trial registration #NCT04350905), we enroll 30 healthy adult participants aged 18 to 45 years of age from Cambodia between October 2020 and January 2021. We perform 3-mm skin biopsies at baseline as well as 30 min, 4 h, and 48 h after a controlled feeding by uninfected Aedes aegypti mosquitos. The primary endpoints are measurement of changes in early and late innate responses in bitten vs unbitten skin by gene expression profiling, immunophenotyping, and cytokine profiling. The results reveal induction of neutrophil degranulation and recruitment of skin-resident dendritic cells and M2 macrophages. As the immune reaction progresses T cell priming and regulatory pathways are upregulated along with a shift to Th2-driven responses and CD8+ T cell activation. Stimulation of participants’ bitten skin cells with Aedes aegypti salivary gland extract results in reduced pro-inflammatory cytokine production. These results identify key immune genes, cell types, and pathways in the human response to mosquito bites and can be leveraged to inform and develop novel therapeutics and vector-targeted vaccine candidates to interfere with vector-mediated disease.
Mosquito-borne viruses are a growing global threat. Initial viral inoculation occurs in the skin via the mosquito ‘bite’, eliciting immune responses that shape the establishment of infection and pathogenesis. To understand these phenomena, we assessed the cutaneous innate and adaptive immune responses via controlled Aedes aegypti feedings in humans living in an Aedes-endemic country. Gene expression profiling and immunophenotyping revealed induction of neutrophil degranulation and recruitment of skin-resident dendritic cells and M2-macrophages. As the immune reaction progressed over time, T cell priming and regulatory pathways were upregulated along with a shift to a Th2-driven response and CD8+ T cell activation. In accordance, participants’ bitten skin cells produced less pro-inflammatory cytokines when stimulated by Ae. aegypti salivary gland extract. These results identify key immune genes, cell types, and pathways in the human response to mosquito bites that can be leveraged to develop novel therapeutics and vector-targeted vaccine candidates to arboviral diseases.Graphical Abstract
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.