PHLEBOTOMUS-PAPATASI SAND FLY SALIVARY-GLAND LYSATE DOWN-REGULATES A TH1, BUT UP-REGULATES A TH2, RESPONSE IN MICE INFECTED WITH LEISHMANIA-MAJOR

A vertebrate host becomes infected with Leishmania major when the sand By vector injects parasites into skin along with saliva. Previous stu dies showed that salivary gland lysate of the New World sand By Lutzom yia longipalpis markedly enhanced L, major infection in CBA mice. Howe ver, L, major is an Old World parasite transmitted in nature by the Ol d World sand By Phlebotomus papatasi, Here we examine the ability of P , papatasi salivary gland lysate to enhance infection (lesion size and parasite burden) by L major, In addition, we examine the effects of s alivary gland lysate on the immune response to L, major by monitoring the levels of cytokine mRNA from the lymph nodes draining cutaneous le sions. We found that P, papatasi salivary gland lysate dramatically ex acerbated lesion development in disease-resistant CBA mice. This exace rbation of disease correlated with inhibition of the production of Th1 cytokines and associated factors (IFN-gamma, IL-12, and inducible nit ric oxide synthase), but with enhancement of the Th1 cytokine IL-4, wh ereas no changes in the levels of IL-10 and TGF-beta were noted, Impor tantly, salivary gland lysate directly up-regulated expression of IL-4 mRNA in mice in the absence of infection with L, major.