The inhibitory effect against collagen-induced arthritis by Schistosoma japonicum infection is infection stage-dependent

Abstract

BackgroundA long-term existing schistosome infection can aid in maintaining immuno-homeostasis, thus providing protection against various types of autoimmune diseases to the infected host. Such benefits have often been associated with acute or egg stage infection and with the egg-induced Th2 response. However, since schistosome infection undergoes different stages, each associated with a specific induction of Th responses, the requirements for the ability of the different stages of schistosome infection to protect against autoimmune disease has not been elucidated. The present study was designed to study whether different stages of schistosome infection offer unique protection in collagen-induced arthritis and its mechanisms.ResultsArthritis susceptible strain DBA/1 male mice were infected with Schistosoma japonicum for either 2 weeks resulting in early stage infection or for 7 weeks resulting in acute or egg stage infection. Following Schistosoma japonicum infection, collagen II was administered to induce collagen-induced arthritis, an animal model for human rheumatoid arthritis. Infection by Schistosoma japonicum significantly reduced the severity and the incidence of experimental autoimmune collagen-induced arthritis. However, this beneficial effect can only be provided by a pre-established acute stage of infection but not by a pre-established early stage of the infection. The protection against collagen-induced arthritis correlated with reduced levels of anti-collagen II IgG, especially the subclass of IgG2a. Moreover, in protected mice increased levels of IL-4 were present at the time of collagen II injection together with sustained higher IL-4 levels during the course of arthritis development. In contrast, in unprotected mice minimal levels of IL-4 were present at the initial stage of collagen II challenge together with lack of IL-4 induction following Schistosoma japonicum infection.ConclusionThe protective effect against collagen-induced arthritis provided by Schistosoma japonicum infection is infection stage-dependent. Furthermore, the ability of schistosomiasis to negatively regulate the onset of collagen-induced arthritis is associated with a dominant as well as long-lasting Th2 response at the initiation and development of autoimmune joint and systemic inflammation.

Helminth Infections and Host Immune Regulation

“…In type II collagen-induced arthritis (CIA), infection with S. mansoni reduced collagen II-specific antibodies and inflammatory cytokine production, while pathology negatively correlated with parasite burden (215). Similarly, S. japonicum was also shown to suppress CIA; however, in a stage-specific manner, earlystage infection (2 weeks postinfection) significantly suppressed arthritis, collagen II-specific antibody titers, and inflammatory cytokine production, while productive egg-laying infection (7 weeks postinfection) had no effect (114). Thus, the schistosome suppression of arthritis pathology may depend on a lack of egg-induced inflammation, as seen in asthma models of S. mansoni infection (186).…”

Helminthotherapy

“…Her iki modelde de, helmintik terapinin T H 2 immün yanıtı tetikleyerek ve T H 1 immün cevabı baskılayarak faydalı olabileceği rapor edilmiş-tir [60][61][62] . RA'nın oluşmasına karşı etkin olduğu gösterilen helmintlere örnek olarak S. mansoni, S. japonicum ve H. polygrus'un yanında H. diminuta verilebilir [60,61,63,64] .…”

“…RA'nın oluşmasına karşı etkin olduğu gösterilen helmintlere örnek olarak S. mansoni, S. japonicum ve H. polygrus'un yanında H. diminuta verilebilir [60,61,63,64] . Bunlardan H. diminuta'nın, CFA aracılı RA'nın indüklemesinden sonra verildiğinde bile, diz şişkinliğini dindirici bir etkisinin olduğu ve iyileşmeyi hızlandırdığı rapor edilmiş-tir [63] .…”

“…Öte yandan, S. mansoni maruziyetine kıyas-la, S. japonicum infeksiyonunun koruyucu etkisi için, kollajen ile sensitizasyon sırasında parazitin yumurtlama evresine erişmiş olmasının gerektiği rapor edilmiştir [61] . Bu, parazitik infeksiyon maruziyetine başlanacağı zamanın da önemli bir faktör olabileceği ve parazitten parazite değişkenlik gös-terebileceği görüşünü desteklemektedir [31] .…”

Parasitic Helminths as Potential Therapeutic Agents Against Autoimmune Disorders

“…Since our publication, other investigators also have demonstrated therapeutic effects of schistosomes on arthritis models. He et al (2010) showed that S.japonicum suppressed CIA. However, infection at 2 weeks before CIA induction resulted in an exacerbation of the disease, whereas infection at 7 weeks before induction prevented the disease.…”