Leishmania donovani: Evolution and architecture of the splenic cellular immune response related to control of infection

Infection with the protozoan Leishmania donovani in humans is usually subcl inical. Parasites probably persist for the life of the host and the low-lev el infection is controlled by the cellular immune response. To better under stand the mechanisms related to the control of infection, we studied the ev olution and architecture of the splenic cellular immune response in a murin e model that is most representative of human subclinical infection. Followi ng systemic inoculation with L. donovani, the parasites were primarily loca lized to the macrophage-rich splenic red pulp. There was art initial increa se in the numbers of T cells and dendritic cells in the periarteriolar lymp hoid sheath and marginal zone, but the red pulp (where parasitized macropha ges were prominent) remained free of these cells until later in the course of infection. Thus, T cells did not colocalize with parasitized red pulp ma crophages until later in the course of infection. Early in the course of in fection, IL-10 production within the marginal zone and TGF-beta production by cells in the red pulp were prominent. These macrophage-inhibitory cytoki nes may contribute to the establishment of the infection and early parasite replication. By day 28 of infection, when the visceral parasite burden beg an to decline, the number of IL-10-producing spleen cells was back to the b aseline level, but IFN-gamma production was higher and the number of IL-12- producing cells was increased dramatically. At this time T cells and dendri tic cells had moved out of the lymphoid follicle and marginal zone into the red pulp where the parasites were located. These findings therefore sugges t that control of infection is associated with IFN-gamma and IL-12 producti on and migration of T cells and dendritic cells to the site of chronic para sitism. (C) 2001 Academic Press.