Leishmania donovani infection in athymic mice derived from parental strains of the susceptible (Lshs) or resistant (Lshr) phenotype.

Abstract

Leishmania donovani, the agent of disseminated leishmaniasis, is a vectortransmitted protozoan parasite which multiplies exclusively within tissue macrophages of the infected host [16,25,39]. The etiologic agent is one of several species responsible for human leishmamasis manifested either by cutaneous or systemic disease [25,391. Visceral leishmaniasis is a chronic and life-threatening infection. The parasite is disseminated from the skin to the liver, spleen, and bone marrow, where macrophages serve as obligatory host cells for the amastigote (tissue) form of Leishmania donovani. The genetic basis for resistance or susceptibility to infection has become amenable to analysis primarily by the development of congenic and recombinant inbred strains of mice for use as experimental hosts [3,6,9,32,35,36]. Less than 10 years ago, Bradley et al [6,8,9] performed seminal studies showing that inbred strains of mice can be classified as innately resistant or susceptible to L donovani by the patterns of infection which ensue after challenge. Resistance or susceptibility as measured by the increase in the total parasite burden in the liver after several weeks of infection reveal that some inbred mouse strains restrict intrahepatic multiplication while others permit significant multiplication within macrophages so that a 10-100-fold increase in L donovani amastigotes is evident within 30 days. It was subsequently established that resistance or susceptibility of mice is controlled by a single autosomal gene on mouse chromosome I [9]. The gene designated as Lsh appears to govern macrophage functions so that significant intracellular multiplication of the protozoan parasite in the liver and spleen is either permitted or restricted