MURINE CUTANEOUS LEISHMANIASIS: DISEASE PATTERNS IN INTACT AND NUDE MICE OF VARIOUS GENOTYPES AND EXAMINATION OF SOME DIFFERENCES BETWEEN NORMAL AND INFECTED MACROPHAGES

Abstract

The course of the disease, cutaneous leismaniasis, caused by the intracellular protozoan parasite Leishmania tropica, differs markedly amongst various common inbred mouse strains. After intradermal injection of 1 10⁶ promastigotes to young female specific pathogen-free (SPF) derived mice, persistent infection characterized by an expanding ulcerous lesion is seen in BALB/c and DBA/2 mice. In the strains CBA/H, C3H/He and A/J, lesions resolve within 8 weeks, and in C57Bl/6 mice no real lesion typical of Cutaneous leishmaniasis develops at the injection site. NZB mice are highly resistant. Macrophages harvested from the thioglycollate-stimulated peritoneal cavity of NZB and C57Bl/6 mice appear to differ from macrophages of the other mouse strains in not supporting multiplication of L. tropica organisms in vitro. Nevertheless, hypothymic nude (nu/nu) mice of C57B1/6 genetype, as well as CBA/H-nu/nu and BALB/c-nu/nu mice, develop large lesions with metastases to other cutaneous and visceral locations. In the intact mice in which infection resolves spontaneously, resistance to reinfection is complete. Using mouse antipromastigote sera and an indirect fluorescent antibody test in carefully controlled experiments, L. tropica antigens were detected on in vitro infected macrophages of both highly susceptible BALB/c and relatively resistant CBA/H genotypes. After incubation with a crude soluble antigen preparation from cultured promastigotes, infected macrophages of both genotypes) in being unable to sensitize syngeneic recipients for a delayed-type hypersensitivity response to that antigen. When infected and uninfected macrophages were used as "blocking cell" in an in vitro alloreactive cytotoxic T cell system involving cells from congenic mice, evidence was obtained for reduced H-2^d expression on infected macrophages of the susceptible mouse strain, BALB/c. The data in this model system of cutaneous leishmaniasis.