Hepatic Granulomas in Murine Visceral Leishmaniasis Caused byLeishmania chagasi

Abstract

Protozoa belonging to the genusLeishmaniacause the diverse forms of human leishmaniasis, which range from self-healing cutaneous ulcers to widely disseminated or disfiguring disease. Human and murine immune responses to species causing cutaneous and visceral leishmaniasis are considerably different. In murine models of cutaneous leishmaniasis the expansion of distinct CD4+T-cell subsets is associated with either disease prevention (TH1) or disease exacerbation (TH2). However, studies of murine visceral leishmaniasis havenotshown expansion of disease-exacerbating cells during progressive disease. The latter studies have concentrated on immune responses in splenocytes from mice infected with visceralizingLeishmaniaspecies, even though the parasites are found primarily in the livers of infected mice. The histologic response to visceralizingLeishmaniasp. in the liver is one of granuloma formation, which proceeds with similar kinetics in resistant C3H and susceptible BALB/c mice. We isolated hepatic granulomas from BALB/c mice infected for 6 weeks with the visceralizing parasiteL. chagasi.Study of dispersed granuloma cells by FACS andin vitrocultivation with antigen showed differences between the responses of immune cells from the spleens and liver granulomas of these infected animals. A careful dissection of immune responses in hepatic granuloma cells from susceptible or resistant mice infected withL. chagasimay lead to a better understanding of murine immune responses to these important pathogens.