In order for the mosquito to obtain a blood meal it must surmount the vertebrate physiological responses. The mosquito, as with all blood-feeding arthropods, has evolved mechanisms to effectively block the hemostasis system with their saliva, which contains a mixture of secreted proteins. Mosquito saliva negatively affects vascular constriction, blood clotting, platelet aggregation, angiogenesis and immunity and creates inflammation.Universally, hematophagous arthropod saliva contains at least one anticlotting, one anti-platelet, and one vasodilatory substance. Mosquito saliva also contains enzymes that aid in sugar feeding and antimicrobial agents to control bacterial growth in the sugar meal. The composition of mosquito saliva is relatively simple as it usually contains fewer than 20 dominant proteins. Despite the great strides in knowledge of these molecules and their role in bloodfeeding achieved recently, scientists still cannot ascribe functions to more than half of the molecules found in arthropod saliva. One promising application is the development of anti-clotting drugs based on saliva molecules, which might be useful for approaching heart-related disease, because they are more user-friendly blood clotting inhibitors and capillary dilators.It is now well recognized that the feeding ticks, sandflies, and, more recently, mosquitoes have an ability to modulate the immune response of the animals (hosts) they feed on.The presence of this activity in vector saliva is a reflection of the inherent overlapping and interconnected nature of the host hemostatic and inflammatory/immunological responses and the intrinsic need to prevent these host defenses from disrupting successful feeding. The mechanism for mosquito saliva-induced alteration of the host immune response is unclear, but the data has become increasingly convincing that such an effect occurs. Early work described a factor in saliva that directly suppresses TNF-α release, but not antigen-induced histamine secretion, from activated mast cells. Experiments by Cross et al. (1994) demonstrated that the inclusion of Ae. aegypti mosquito saliva into naïve cultures led to a suppression of interleukin (IL)-2 and IFN-γ production, while the cytokines IL-4 and IL-5 are unaffected by mosquito saliva. Cellular proliferation in response to IL-2 is clearly reduced by prior treatment of cells with SGE.Correspondingly, activated splenocytes isolated from mice fed upon by either Ae. aegypti or Cx. pipiens mosquitoes produce markedly higher levels of IL-4 and IL-10 concurrent with suppressed IFN-γ production. Unexpectedly, this shift in cytokine expression is observed in splenocytes up to 10 days after mosquito exposure, suggesting that natural feeding of mosquitoes can have a profound, enduring, and systemic effect on the immune response.
T cell populations are decidedly susceptible to the suppressive effect of mosquito saliva, showing enhanced mortality and decreased division rates.Parallel work by Wasserman et al. (2004) demonstrated that T- and B-cell proliferation was inhibited in a dose dependent manner with concentrations as low as 1/7th of the saliva in a single mosquito.Depinay et al. (2005) observed a suppression of antibody-specific T cell responses mediated by mosquito saliva and dependent on mast cells and IL-10 expression.A recent study suggests that mosquito saliva can also decrease expression of interferon−α/β during early mosquito-borne virus infection.The contribution of type I interferons (IFN) in recovery from infection with viruses has been demonstrated in vivo by the therapeutic and prophylactic effects of administration of IFN-inducers or IFN,and recent research suggests that mosquito saliva exacerbates West Nile virus infection,as well as other mosquito-transmitted viruses.
