The Schistosome Granuloma: Characterization of Lymphocyte Migration, Activation, and Cytokine Production

Abstract

Granuloma formation and its regulation are dependent on lymphocytes. Therefore, we compared the characteristics of lymphocytes derived from the spleens and granulomas of Schistosoma mansoni-infected mice during the course of their disease. We examined lymphocyte cell cycle kinetics, migration, expression of activation Ags (CD69 and IL-2R), cytokine production (IL-2, IL-4, IFN-γ), and apoptosis. Lymphocytes in the G2/M phase of the cell cycle and high levels of lymphocyte intracellular IL-2 were found in the spleen but not in the granuloma. Cell trafficking experiments showed Ag-specific recruitment of schistosomal egg Ag (SEA)-reactive lymphoblasts into granulomas in vivo, as well as recruitment to, residence within, and egress from granulomas in vitro. Granuloma-derived lymphocytes were more highly activated than splenic lymphocytes based on higher levels of CD69 and IL-2R expression. While the granuloma microenvironment was rich in Th2 cytokines, during peak granuloma formation, the lymphocytes per se from the spleen and granuloma did not exhibit a dominant Th1 or Th2 cytokine profile, producing low but similar levels of IL-4 and IFN-γ. The discrepancy between high IL-2R expression and low levels of IL-2 protein production by granuloma lymphocytes was associated with increased apoptosis in the granuloma compared with the spleen. These findings support the hypothesis that granulomas may play a role in the regulation of systemic pathology in schistosomiasis by adversely affecting the survival of SEA-reactive, immunopathogenic T lymphocytes.

Detection of cytological abnormalities in urothelial cells from individuals previously exposed or currently infected with Schistosoma haematobium

“…This could be due to bladder injury and disruptions to the urothelium. This is consistent with a recent report that described a case of urinary schistosomiasis where histopathology revealed male and female worms in the bladder together with active granulomas and intense inflammatory cells infiltration consisting mainly of polymorphonuclear cells and lymphocytes [ 16 ]. The presence of lymphocytes is also characteristic of the formation of granulomas due to the S .…”

“…haematobium infection. The granuloma forms around the eggs of parasite and prevent their release into the bladder and subsequent excretion [ 16 , 28 , 29 ]. In addition to PMNs and lymphocytes there was also an increase in normal and reactive urothelial cells as well as squamous cells.…”

“…During the infection, the ova embed in the bladder epithelium (BE) and secrets soluble egg antigen that modulate the immune system resulting in the recruitment of inflammatory cells and secretion of inflammatory mediators eventually leading to the formation of a granuloma around the egg [ 16 – 19 ]. At the same time, the parasite activity in the BE causes its shedding.…”