DEVELOPMENT OF A NATURAL MODEL OF CUTANEOUS LEISHMANIASIS - POWERFUL EFFECTS OF VECTOR SALIVA AND SALIVA PREEXPOSURE ON THE LONG-TERM OUTCOME OF LEISHMANIA-MAJOR INFECTION IN THE MOUSE EAR DERMIS

We have developed a model of cutaneous leishmaniasis due to Leishmania major that seeks to mimic the natural conditions of infection. 1,000 metacyclic promastigotes were coinoculated with a salivary gland sonic ate (SGS) obtained from a natural vector, Phlebotomus payatasii, into the ear dermis of naive mice or of mice preexposed to SGS. The studies reveal a dramatic exacerbating effect of SGS on lesion development in the dermal site, and a complete abrogation of this effect in mice pre exposed to salivary components. In both BALB/c and C57B1/6 (B/6) mice, the dermal lesions appeared earlier, were more destructive, and conta ined greater numbers of parasites after infection ill the presence of SGS. Furthermore, coinoculation of SGS converted B/6 mice into a nonhe aling phenotype. No effect of SGS was seen in either IL-4-deficient or in SCID mice. Disease exacerbation in both BALB/c and B/6 mice was as sociated with an early (6 h) increase in the frequency of epidermal ce lls producing type 2 cytokines. SGS did not elicit type 2 cytokines in the epidermis of mice previously injected with SGS. These mice made a ntisaliva antibodies that were able to neutralize the ability of SGS t o enhance infection and to elicit IL-4 and IL-5 responses in the epide rmis. These results are the first to suggest that for individuals at r isk of vector-borne infections, history of exposure to vector saliva, might influence the outcome of exposure to transmitted parasites.