title: Impact of Schistosoma japonicum infection on collagen-induced arthritis in DBA/1 mice: a murine model of human rheumatoid arthritis.
abstract: BACKGROUND
  The hygiene hypothesis suggests that helminth infections prevent a range of autoimmune diseases.
  
  
  RESULTS
  To investigate the effects of S. japonicum infection on collagen-induced arthritis (CIA), male DBA/1 mice were challenged with unisexual or bisexual S. japonicum cercariae two weeks prior to bovine type II collagen (CII) immunization or at the onset of CIA. S. japonicum infection prior to CII immunization significantly reduced the severity of CIA. ELISA (enzyme linked immunosorbent assay) showed that the levels of anti-CII IgG and IgG2a were reduced in prior schistosome-infected mice, while anti-CII IgG1 was elevated. Splenocyte proliferation against both polyclonal and antigen-specific stimuli was reduced by prior schistosome infection as measured by tritiated thymidine incorporation ((3)H-TdR). Cytokine profiles and CD4(+) T cells subpopulation analysis by ELISA and flow cytometry (FCM) demonstrated that prior schistosome infection resulted in a significant down-regulation of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β and IL-6) and Th1 cells, together with up-regulation of the anti-inflammatory cytokine IL-10 and Th2 cells. Interestingly, the expansion of Treg cells and the reduction of Th17 cells were only observed in bisexually infected mice. In addition, prior schistosome infection notably reduced the expression of pro-inflammatory cytokines and receptor activator of NF-κB ligand (RANKL) in the inflamed joint. However, the disease was exacerbated at one week after infection when established CIA mice were challenged with bisexual cercariae.
  
  
  CONCLUSIONS
  Our data provide direct evidence that the Th2 response evoked by prior S. japonicum infection can suppress the Th1 response and pro-inflammatory mediator and that bisexual infection with egg-laying up-regulates the Treg response and down-regulates the Th17 response, resulting in an amelioration of autoimmune arthritis. The beneficial effects might depend on the establishment of a Th2-dominant response rather than the presence of the eggs. Our results suggest that anti-inflammatory molecules from the parasite could treat autoimmune diseases.
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Song
authors.forename: Jilong
authors.initials: J
authors.lastname: Shen
authors.forename: Huiqin
authors.initials: H
authors.lastname: Wen
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Zhong
authors.forename: Qinli
authors.initials: Q
authors.lastname: Luo
authors.forename: Deyong
authors.initials: D
authors.lastname: Chu
authors.forename: Yao
authors.initials: Y
authors.lastname: Qi
authors.forename: Yuanhong
authors.initials: Y
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D024043:Collagen Type II / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D061148:Hygiene Hypothesis; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D012549:Schistosoma japonicum / Q000276:immunology* / Q000469:parasitology; D012554:Schistosomiasis japonica / Q000276:immunology*; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D061147:Therapy with Helminths
chemical_list: D000888:Antibodies, Anti-Idiotypic; D024043:Collagen Type II; C048844:anti-IgG; D015847:Interleukin-4; D007371:Interferon-gamma