Host-parasite relationship in murine leishmaniasis: pathophysiological and immunological changes.
The host-parasite relationship in human visceral leishmaniasis remains poorly understood. In the present study, pathophysiological and immunological changes were examined in BALB/c mice infected with Leishmania donovani. These animals developed chronic infection with massive hepatosplenomegaly and hypergammaglobulinemia. In contrast to mice inoculated with 0.8 X 10(6) or 4 X 10(6) amastigotes, mice infected with 20 X 10(6) amastigotes failed to reduce liver parasite loads during 2 to 8 weeks of observation. At 8 weeks, liver size was increased by 26, 63, and 94%, respectively, in groups infected with 0.8 X 10(6), 4 X 10(6), or 20 X 10(6) amastigotes. Serum immunoglobulin G and M levels at 8 weeks in animals with the heaviest infection were increased by 53 and 80%, respectively, compared with controls. Specific antileishmanial antibodies were detected in the absence of antigen-specific delayed-type hypersensitivity or in vitro lymphocyte responses. Infection did not suppress the in vivo responses of mice to the non-parasite-related antigens sperm whale myoglobin or pneumococcal polysaccharide. Splenic mononuclear cell responses to phytohemagglutinin were suppressed as early as 2 weeks, and by 8 weeks, mice infected with 0.8 X 10(6), 4 X 10(6), or 20 X 10(6) amastigotes had phytohemagglutinin responses which were, respectively, 27.7, 13.9, and 15.8% of controls. Decreased phytohemagglutinin responses could not be related to reductions in splenic T cells; however, splenic B cells and macrophages were increased at 8 weeks of infection. The course of L. donovani infection and disease in BALB/c mice resembles events occurring in humans and should prove useful in defining mechanisms of immune alterations in visceral leishmaniasis.
D000818:Animals; D000906:Antibodies / Q000032:analysis; D002452:Cell Count; D006790:Host-Parasite Interactions; D006968:Hypersensitivity, Delayed; D007114:Immunization; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007891:Leishmania / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000473:pathology; D008099:Liver / Q000469:parasitology; D008213:Lymphocyte Activation; D008264:Macrophages; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000473:pathology
D000906:Antibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M