Sand fly vector saliva selectively modulates macrophage functions that inhibit killing of Leishmania major and nitric oxide production

Abstract

The saliva of Phlebotomus papatasi, a sand fly vector for Leishmania major, contains a factor that exacerbates leishmaniasis and may be required for the establishment of infection with Leishmania in nature. We have examined the effect of sand fly saliva on various macrophage functions in vitro. Our data demonstrate that although saliva does not alter uptake of L. major by macrophages, it inhibits the ability of IFN-gamma 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. Furthermore, this inhibition of parasite destruction correlates with reduction of nitric oxide (NO) production, suggesting that the ability of sand fly saliva to reduce nitrogen oxidation in response to IFN-gamma may be responsible for the inhibitory effect of saliva on intracellular killing of L. major. Finally, despite the fact that saliva inhibits NO production in IFN-gamma-activated macrophages, it does not prevent IFN-gamma from up-regulating class II MHC expression on macrophages. This suggests that the immunosuppressive effect of sand fly saliva on the macrophage is targeted to certain critical, but not all, functions of the cell.