Hepatic Granulomas in Murine Visceral Leishmaniasis Caused by Leishmania chagasi

Protozoa belonging to the genus Leishmania cause 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 have not shown expansion of disease-exacerbating cells during progressive disease. The latter studies have concentrated on immune responses in splenocytes from mice infected with visceralizing Leishmania species, even though the parasites are found primarily in the livers of infected mice. The histologic response to visceralizing Leishmania sp. 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 parasite L. chagasi. Study of dispersed granuloma cells by FACS and in vitro cultivation 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 with L. chagasi may lead to a better understanding of murine immune responses to these important pathogens.