The formation of egg granulomas in the spleens of mice with late Schistosoma japonicum infection alters splenic morphology

Abstract

BackgroundSplenomegaly is a characteristic symptom of schistosome infection. Unlike the well known hepatic pathology of schistosomiasis, splenomegaly has received little scientific research and is generally considered to be a non-specific congestion caused by increased blood pressure within the venous sinuses. Moreover, to date, few studies have reported the deposition of schistosome eggs in the spleen. In a previous study, however, we observed that prolonged S. japonicum infections destroyed the structure of the lymphoid follicles in the spleen of mice at 8 weeks post-infection and found that eggs were frequently deposited in the spleen. These prior observations suggested a relationship between granulomas and splenic morphology which we investigate further in this study.MethodsC57BL/6 mice were infected percutaneously with twenty cercariae of S. japonicum and sacrificed at different times post-infection. The number of eggs present in the homogenates of spleens and livers was quantified by light microscopy. Splenic pathology was observed by immunohistochemistry staining of paraffin-embedded sections. At 18 weeks post-infection the infected mice were divided into two groups (granulomatous spleens and non-granulomatous spleens). Serum antibodies and cytokines in the antigen- or mitogen-stimulated lymphocyte cultures were then determined by ELISA.ResultsWe found that eggs deposition in the spleens of infected mice occurred frequently but only occasionally led to granulomas formation. The lymphoid follicles within the granulomatous spleens maintained their structural integrity until 20 weeks post-infection, unlike the lymphoid follicles in spleens without egg granulomas. Mice with granulomatous spleens accompanied by lymphoid follicles exhibited a germinal center (GC)-like structure and had enhanced humoral immune responses. Splenocytes from granulomatous spleens also showed significantly elevated levels of Th2 cytokines during late infection stages.ConclusionsOur results highlight that lymphoid follicles, which are not completely destroyed or are re-established in the spleen, can change the local immune environment and lead to changes in the splenic morphology of mice with chronic schistosomiasis.

Histological study on the possible therapeutic role of bone marrow derived mesenchymal stem cells in a model of Schistosoma mansoni infestation of spleen of mice

“…Some cells with many dilated cisternae of rough endoplasmic reticulum denoting activated cells secreting cytokines and cells with degenerative changes were also detected. These results were in accordance with [21,22] who explained that eggs deposition constitutes the major pathogenesis of schistosomiasis, with egg-laying beginning four weeks after infestation and reaching a peak at eight weeks post-infestation. Furthermore, Skelly [23] postulated that in contrast to the adult worms, parasite eggs via soluble egg antigen (SEA) provoked a potent chemotactic activity and strong inflammatory reaction resulting in stimulation of inflammatory cells and cytokines (including interferon-γ, TNF-α and ILs).…”

“…Instead, the granulomas were replaced by leucocytic (eosinophils) infiltration. This was in accordance with other investigators [21] as they explained that as the disease advances from the acute to the chronic stage, granulomas decrease in both size and cellularity because of immune regulation. Classically, the host initially responds with a (Th1) response which was directed against initial stages of the parasite.…”

NP30 stimulates Th17 differentiation through DC in Schistosomiasis Japonicum

“…During the past few years, many studies have proven that through the expression of chemokines and the secretion of cytokines, the responses of Th17 cells dominate and play key roles in the host defence in response to S. japonicum . Because Th17 has become an important supplement to Th1/Th2 paradigm, we must ask the question of whether or not NP30 can direct Th17 differentiation.…”

“…During the acute stage of S. japonicum infection, schistosome antigens induce Th1‐dominant cell‐mediated immune response in the host. During the chronic infection stage, Th1‐type cellular immunity shifts to Th2‐type cellular immunity . Particularly, some recent studies have revealed that Th17 cells play crucial roles in the pathology in schistosomiasis .…”

“…During the chronic infection stage, Th1-type cellular immunity shifts to Th2-type cellular immunity. 10 Particularly, some recent studies have revealed that Th17 cells play crucial roles in the pathology in schistosomiasis. 11 Moreover, in the context of severe egg-induced immunopathology, this differentiation of Th17 cells stimulates antigen-presenting cells (APCs) to secret some pro-inflammatory cytokines.…”