Leishmania tropica:The Identification and Purification of Metacyclic Promastigotes and Use in Establishing Mouse and Hamster Models of Cutaneous and Visceral Disease

Abstract

Lira, R., Méndez, S., Carrera, L., Jaffe, C., Neva, F., and Sacks, D. 1998.Leishmania tropica:The identification and purification of metacyclic promastigotes and use in establishing mouse and hamster models of cutaneous and visceral disease.Experimental Parasitology89,331–342. Few experimental studies onLeishmania tropicahave been undertaken despite the importance of this parasite as the cause of cutaneous leishmaniasis, and now visceral disease, in the Old World. In part, this is due to the absence of convenient animals models, especially mice, forL. tropicainfections. An anti-lipophosphoglycan (LPG) monoclonal antibody XCIV 1H2-A8 (T11), specific forL. tropica,was found to distinguish between culture-derived procyclic and metacyclic promastigotes. The antibody was used to negatively select for nonagglutinated metacyclic forms in stationary cultures, and the exceptional virulence of the purified metacyclics was verified by their infectivity for mouse macrophagesin vitroand by their ability to produce cutaneous lesions in footpads of BALB/c mice. The lesions produced by three cutaneous isolates ofL. tropicawere nonulcerative and nonprogressive. Nonetheless, the lesions failed to heal, and high numbers of parasites could be recovered from footpads and draining lymph nodes up to 9 months after infection. Infections usingL. tropicametacyclics purified from cutaneous, visceral and viscerotropic (Desert Storm) isolates ofL. tropicawere compared in both mouse and hamster models. Differences in disease progression were found that may reflect the parasite tissue tropism and virulence displayed by these strains in their human hosts. These findings suggest a role for parasite-related determinants in the clinical spectrum of disease.