Infection pattern and immune response in the spleen and liver of BALB/c mice intracardially infected with Leishmania donovani amastigotes.

Intracardial inoculation of BALB/c mice with Leishmania donovani amastigotes induced progressive visceral leishmaniasis (VL) with increasing splenic parasite load when followed upto 4-month postinfection period. In contrast, the liver parasite load reached maximum around 2-month postinfection period following which it started declining. The infection pattern differed somewhat from the earlier reports on mouse model of VL induced by intravenous inoculation of parasites with respect to the duration as well as magnitude of parasite burden in the organs (liver and spleen) and associated hepatosplenomegaly. Immunosuppression in mice with progressive VL was manifested in the form of impairment of proliferative response of the splenic mononuclear cells (SPMC) to in vitro stimulation with leishmanial antigen or the mitogen concanavalin A (ConA), although ConA stimulated cells were found to be capable of IL-2 and IFN-gamma synthesis. Differential expression of activating (IL-2, IFN-gamma and TNF-alpha) as well as deactivating (IL-4 and TGF-beta) cytokines was demonstrable in the spleen and liver of animals during the course of infection. Further, the synthesis of inducible nitric oxide synthase (iNOS) enzyme increased considerably in the liver as well as in the spleen of 4-month infected animal with parallel increase in the transcripts of the iNOS activating cytokines IFN-gamma and TNF-alpha. The temporal variation in the organ specific immune response could be related to the differential control of parasite burden in the liver and spleen of the infected host.