Experimental Cutaneous Leishmaniasis: Disseminated Leishmaniasis in Genetically Susceptible and Resistant Mice *

Abstract

Abstract Leishmania tropica infections in mice provide models for the study of non-healing leishmanial infections similar to diffuse cutaneous leishmaniasis (DCL) in man. BALB/c mice infected with L. tropica developed large non-healing primary lesions as well as multiple metastatic lesions on the feet, face and ears. This susceptibility was not dose- or route-dependent. In contrast, C57BL/6 mice, when inoculated intradermally (ID), developed cutaneous lesions which healed. However, when the normally resistant C57BL/6 mice were inoculated intravenously (IV), they developed multiple non-healing lesions which resembled the infection seen in susceptible BALB/c mice. Thus, non-healing leishmanial infections similar to those of human DCL can be produced in both a genetically susceptible (BALB/c) and resistant (C57BL/6) strain of mouse. Although the eventual outcome of the infection is similar in BALB/c and IV inoculated C57BL/6 mice, the immunological parameters of the infection in the two models differed significantly. L. tropica infection in BALB/c mice was associated with a non-specific immunodepression, as assessed by lymphocyte proliferative responses to concanavalin A, phytohemagglutinin and lipopolysaccharide. In contrast, no evidence of generalized immunodepression was observed in the IV-inoculated, non-healing C57BL/6 mice. These two models also differed in their ability to express a delayed skin response to leishmanial antigen during infection. BALB/c mice were capable of mounting a transient delayed skin response, while IV-inoculated C57BL/6 mice developed no detectable delayed hypersensitivity. Both non-healing and healing infections were accompanied by the development of specific indirect immunofluorescent antibody, although the titers were significantly higher in non-healing infections. Spleen cells from infected BALB/c and C57BL/6 (ID- or IV-inoculated) mice responded to leishmanial antigen in a lymphocyte transformation assay. In BALB/c mice the ability to respond to antigen could be demonstrated throughout the course of infection; however, non-healing C57BL/6 mice developed a suppressor cell late in the infection which suppressed leishmanial antigen responses.