The enhancement of arbovirus transmission and disease by mosquito saliva is associated with modulation of the host immune response

Abstract

SUMMARYArthropod-borne viruses have emerged as a major human health concern. Viruses transmitted by mosquitoes are the cause of the most serious and widespread arbovirus diseases worldwide and are ubiquitous in both feral and urban settings. Arboviruses, including dengue and West Nile virus are injected into vertebrates within mosquito saliva during mosquito feeding. Mosquito saliva contains anti-haemostatic, anti-inflammatory and immunomodulatory molecules that facilitate the acquisition of a blood-meal. Collectively, studies investigating the effects of mosquito saliva on the vertebrate immune response suggest that at high concentrations salivary proteins are immmunosuppressive, whereas lower concentrations modulate the immune response; specifically, T H 1 and antiviral cytokines are down-regulated, while T H 2 cytokines are unaffected or amplified. As a consequence, mosquito saliva can impair the anti-viral immune response thus affecting viral infectiousness and host survival. Mounting evidence suggests that this is a mechanism whereby arbovirus pathogenicity is enhanced. In a range of disease models, including various hosts, mosquito species, and arthropodborne viruses, mosquito saliva and/or feeding is associated with a potentiation of virus infection. Compared to arbovirus infection initiated in absence of the mosquito or its saliva, infection including mosquito saliva leads to an increase in virus transmission, host susceptibility, viraemia, disease progression, and mortality.Keywords arthropod-borne virus; mosquito saliva; immunomodulation; disease enhancement Most arthropod-borne (arbo)viruses of public health significance are mosquito-borne, and thus transmitted to vertebrates via the feeding of an infected mosquito. For a mosquito to

INDIVIDUAL HUMAN SERA RESPONSE AGAINST PROTEIN EXTRACTS FROM SALIVARY GLAND OF <i>Aedes aegypti</i>

“…aegypti were co-inoculated with Sindbis virus into mice would increase the immune response toward the Th2 (IL4 and in IL-10 cytokines were increase), whereas the IFNχ and IFNβ were significantly decreased. Similar results were reported by Schneider & Higgs (2008) in which a high concentration of salivary proteins was found to be immmunosuppressive.…”

Dermatologic Changes Induced by RepeatedIxodes scapularisBites and Implications for Prevention of Tick-Borne Infection

“…Although the first study to report that host immunity to the bite of pathogen-free blood-feeding arthropods conferred resistance to subsequent pathogen transmission was one that involved ticks (Bell 1979), the same principles of arthropod-induced immunity also might be extended to vaccination for other arthropod-borne agents, including the strong delayed-type cutaneous hypersensitivity response to sand fly bites that is associated with reduced transmission of Leishmania parasites (Valenzuela et al 2000). A clear link exists between mosquito modulation of host innate and specific acquired immune defenses and enhanced transmission and establishment of arboviruses (Schneider and Higgs 2008). Prior exposure of BALB/c mice to bites of uninfected Anopheles stephensi led to reduced parasitemia following subsequent mosquito transmission of Plasmodium yoelii malaria parasites (Donovan et al 2007).…”

The contribution of rodent models to the pathological assessment of flaviviral infections of the central nervous system

“…Mosquito saliva has been shown to modulate immune cell infiltration at the site of inoculation and reduce the expression of Th1 cytokines and TLR3 [150,174]. However, the adoption of this more natural route of inoculation for virulence studies in vertebrate animals is curtailed by the inherent variability of the infecting dose delivered by individual mosquitoes, the inability to increase the titer of the inoculum, and the potential for selection of mutations in the virus by mosquito passage.…”