Mosquito feeding modulates Th1 and Th2 cytokines in flavivirus susceptiblemice: an effect mimicked by injection of sialokinins, but not demonstratedin flavivirus resistant mice

Culex pipiens and Aedes aegypti mosquitoes were fed on C3H/HeJ mice and sys temic cytokine production was quantified from stimulated lymphocytes harves ted four to ten days after feeding, Mosquito Seeding on C3H/HeJ mice signif icantly down regulated IFN gamma production seven to ten days post feeding by Cx. pipiens and seven days after Ae aegypti feeding. Th2 cytokines, IL-4 and IL-10, were significantly up regulated 4-7 days after Cx, pipiens and Ae. aegypti feeding. The immunosuppressive effect of Cx, pipiens Seeding on systemic cytokine production was not evident in congenic flavivirus resist ant (C3H/RV) mice, as systemic IFN gamma and IL-2 were significantly rip re gulated at days 7 and 10, correlating,vith a significant decrease in IL-4 1 0 days after feeding by Cx. pipiens mosquitoes. Inoculation of 5-1000 ng of sialokinin-I into C3H/HeJ mice mimicked the effect of Ae. aegypti feeding by down regulating Th1 cytokines and significantly rip regulating Th2 cytok ines four days post inoculation, Injections of sialokinin-II resulted in on ly moderate effects on IFN gamma and IL-4 production seven and ten days aft er injection. Thus natural feeding by two arbovirus vectors had a profound T cell modulatory effect in vivo in virus susceptible animals which was not demonstrated in the flavivirus resistant host. Moreover, sialokinin-I and sialokinin-II mimicked the effect of mosquito feeding by modulating the hos t T cell response. These results may lend new insight into specific aspects of the role of the mosquito vector in potentiating virus transmission in t he mammalian host.