title: The formation of egg granulomas in the spleens of mice with late Schistosoma japonicum infection alters splenic morphology.
abstract: BACKGROUND
  Splenomegaly 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.
  
  
  METHODS
  C57BL/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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention; Laboratory of Parasite and Vector Biology, MOH, Shanghai, China. wangyanjuan1036@126.com.|WHO Collaborating Center for Malaria, Schistosomiasis and Filariasis, Shanghai, 200025, PR China. wangyanjuan1036@126.com.
authors.forename: Yanjuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention; Laboratory of Parasite and Vector Biology, MOH, Shanghai, China. silkfan@126.com.|WHO Collaborating Center for Malaria, Schistosomiasis and Filariasis, Shanghai, 200025, PR China. silkfan@126.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention; Laboratory of Parasite and Vector Biology, MOH, Shanghai, China. chart2543@163.com.|WHO Collaborating Center for Malaria, Schistosomiasis and Filariasis, Shanghai, 200025, PR China. chart2543@163.com.
authors.forename: Jianhai
authors.initials: J
authors.lastname: Yin
authors.affiliation: National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention; Laboratory of Parasite and Vector Biology, MOH, Shanghai, China. amyshyj12@163.com.|WHO Collaborating Center for Malaria, Schistosomiasis and Filariasis, Shanghai, 200025, PR China. amyshyj12@163.com.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention; Laboratory of Parasite and Vector Biology, MOH, Shanghai, China. wangying1162@163.com.|WHO Collaborating Center for Malaria, Schistosomiasis and Filariasis, Shanghai, 200025, PR China. wangying1162@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention; Laboratory of Parasite and Vector Biology, MOH, Shanghai, China. ipdxuyx@163.com.|WHO Collaborating Center for Malaria, Schistosomiasis and Filariasis, Shanghai, 200025, PR China. ipdxuyx@163.com.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Xu
authors.affiliation: National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention; Laboratory of Parasite and Vector Biology, MOH, Shanghai, China. caojp@yahoo.com.|WHO Collaborating Center for Malaria, Schistosomiasis and Filariasis, Shanghai, 200025, PR China. caojp@yahoo.com.
authors.forename: Jianping
authors.initials: J
authors.lastname: Cao
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology*; D058487:Cercaria; D016207:Cytokines / Q000097:blood; D006099:Granuloma / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D008099:Liver / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010063:Ovum; D012549:Schistosoma japonicum / Q000276:immunology* / Q000302:isolation & purification; D012554:Schistosomiasis japonica / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D013154:Spleen / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D013163:Splenomegaly / Q000276:immunology / Q000469:parasitology / Q000473:pathology
chemical_list: D000909:Antibodies, Helminth; D016207:Cytokines