ABSTRACT
Leishmania promastigotes are introduced into the skin by blood-sucking phlebotomine sand flies. In the vertebrate host, promastigotes invade macrophages, transform into amastigotes and multiply intracellularly. Sand fly saliva was shown to enhance the development of cutaneous leishmaniasis lesions by inhibiting some immune functions of the host macrophages. This study demonstrates that sand fly saliva promotes parasite survival and proliferation. First, macrophages gravitated towards increasing concentrations of sand fly saliva in vitro. Secondly, saliva increased the percentage of macrophages that became infected with Leishmania promastigotes and exacerbated the parasite load in these cells. Thus, during natural transmission, saliva probably reduces the exposure of promastigotes to the immune system by attracting macrophages to the parasite inoculation site and by accelerating the entry of promastigotes into macrophages. Saliva may also enhance lesion development by shortening the generation time of dividing intracellular amastigotes.
Subject(s)
Leishmania/pathogenicity , Macrophages, Peritoneal/parasitology , Psychodidae/parasitology , Saliva , Animals , Cells, Cultured , Chemotaxis , Female , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Psychodidae/immunologyABSTRACT
As they probe the skin for blood, sand flies inject saliva that prevents hemostasis. Sand fly saliva also promotes leishmaniasis by suppressing immunologic functions of macrophages. Saliva of Phlebotomus papatasi, the vector of Old World cutaneous leishmaniasis, contains adenosine and AMP. We show that Ph. papatasi saliva as well as pure adenosine down-regulate the expression of the inducible nitric oxide (NO) synthase gene in activated macrophages. In addition Ph. papatasi, but not Lutzomyia longipalpis, saliva inhibits the production of NO. Taken together, these data suggest that salivary adenosine is responsible for the down-regulation of NO synthesis. Saliva of both genera Phlebotomus and Lutzomyia contains significant levels of endogenous protein phosphatase-1/2A-like activity that is heat labile, inhibitable by okadaic acid and calyculine a, and does not require divalent cations.
