The inhibitory effect against collagen-induced arthritis by Schistosoma japonicum infection is infection stage-dependent
The inhibitory effect against collagen-induced arthritis by Schistosoma japonicum infection is infection stage-dependent
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DOI：
10.1186/1471-2172-11-28
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发表时间：
2010-06-10
期刊：
影响因子：
3
通讯作者：
Chen, Xiao-Ping
中科院分区：
文献类型：
--
作者：
He, YunKun;Li, Jia;Chen, Xiao-Ping
背景：长期存在的血吸虫感染有助于维持免疫平衡，从而为受感染的宿主提供对各种类型的自身免疫性疾病的保护。这种益处通常与急性或卵期感染以及卵细胞诱导的Th2反应有关。然而，由于血吸虫感染经历了不同的阶段，每个阶段都与特定的Th反应的诱导有关，因此对血吸虫感染的不同阶段预防自身免疫性疾病的能力的要求尚未阐明。本研究旨在探讨不同阶段的血吸虫感染对胶原性关节炎是否具有独特的保护作用及其机制。结果：日本血吸虫感染DBA/1雄性小鼠2周可致早期感染，7周可致急性感染或虫卵感染。日本血吸虫感染后，应用II型胶原诱导胶原诱导的关节炎，这是一种人类类风湿性关节炎的动物模型。日本血吸虫感染显著降低了实验性自身免疫性胶原性关节炎的严重程度和发病率。然而，这种有益的效果只能通过预先确定的感染急性期提供，而不能通过预先确定的感染早期阶段提供。对胶原性关节炎的保护与抗II型胶原免疫球蛋白水平的降低有关，尤其是IgG2a亚类。此外，在受保护的小鼠中，在注射II型胶原时IL-4水平升高，同时在关节炎发展过程中IL-4水平持续升高。结论：日本血吸虫感染对胶原性关节炎的保护作用依赖于感染阶段。此外，血吸虫病负性调节胶原诱导的关节炎的发生的能力与自身免疫性关节和全身性炎症的启动和发展中的主导和持久的Th2反应有关。
Background: A 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.Results: Arthritis 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 preestablished 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.Conclusion: The 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.