SAND FLY VECTOR SALIVA SELECTIVELY MODULATES MACROPHAGE FUNCTIONS THAT INHIBIT KILLING OF LEISHMANIA-MAJOR AND NITRIC-OXIDE PRODUCTION

The saliva of Phlebotomus papatasi, a sand fly vector for Leishmania m ajor, contains a factor that exacerbates leishmaniasis and may be requ ired for the establishment of infection with Leishmania in nature, We have examined the effect of sand fly saliva on various macrophage func tions in vitro, Our data demonstrate that although saliva does not alt er uptake of L. major by macrophages, it inhibits the ability of IFN-g amma to activate macrophages to kill the intracellular parasite, This inhibition of parasite killing is observed when both the promastigote and amastigote forms of the parasite are used for infection, Furthermo re, this inhibition of parasite destruction correlates with reduction of nitric oxide (NO) production, suggesting that the ability of sand f ly saliva to reduce nitrogen oxidation in response to IFN-gamma may be responsible for the inhibitory effect of saliva on intracellular kill ing of L. major, Finally, despite the fact that saliva inhibits NO pro duction in IFN-gamma-activated macrophages, it does not prevent IFN-ga mma from up-regulating class II MHC expression on macrophages, This su ggests that the immunosuppressive effect of sand fly saliva on the mac rophage is targeted to certain critical, but not all, functions of the cell.