La Flamme Anne Camille, Ruddenklau Kate, Bäckström B Thomas
School of Biological Sciences, Victoria University of Wellington, New Zealand.
Infect Immun. 2003 Sep;71(9):4996-5004. doi: 10.1128/IAI.71.9.4996-5004.2003.
A preestablished infection with the parasitic helminth, Schistosoma mansoni, significantly reduced the incidence and delayed the onset of experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice immunized with myelin oligodendrocyte glycoprotein (MOG)(35-55) peptide. The altered disease progression was not solely due to the induction of a strong Th2 response, since intraperitoneal injection of schistosome eggs did not affect disease development. MOG-specific gamma interferon (IFN-gamma), nitric oxide, and tumor necrosis factor alpha production by splenocytes was significantly reduced in schistosome-infected mice compared to uninfected mice. However, similar levels of interleukin-10 (IL-10) were produced in an antigen-specific manner, suggesting that the induction of antigen-specific responses was not inhibited. Analysis of in vivo cytokine production by real-time PCR indicated that IL-12p40, but not IFN-gamma, transcript levels were dramatically reduced in the spinal cords of schistosome-infected, MOG-immunized mice. Furthermore, analysis of the cellular composition of the spinal cords and brains revealed that a preestablished infection with S. mansoni decreased central nervous system (CNS) inflammation, particularly of macrophages and CD4 T cells. These results suggest that schistosomiasis may negatively regulate the onset of EAE by downregulating the production of proinflammatory cytokines and altering CNS inflammation.
预先感染寄生性蠕虫曼氏血吸虫,可显著降低用髓鞘少突胶质细胞糖蛋白(MOG)(35 - 55)肽免疫的C57BL / 6J小鼠实验性自身免疫性脑脊髓炎(EAE)的发病率,并延迟其发病。疾病进展的改变并非仅仅由于诱导了强烈的Th2反应,因为腹腔注射血吸虫卵并不影响疾病发展。与未感染小鼠相比,血吸虫感染小鼠脾细胞产生的MOG特异性γ干扰素(IFN-γ)、一氧化氮和肿瘤坏死因子α显著减少。然而,以抗原特异性方式产生的白细胞介素-10(IL-10)水平相似,表明抗原特异性反应的诱导未受抑制。通过实时PCR分析体内细胞因子产生情况表明,在感染血吸虫且用MOG免疫的小鼠脊髓中,IL-12p40转录水平显著降低,但IFN-γ转录水平未降低。此外,对脊髓和脑的细胞组成分析显示,预先感染曼氏血吸虫可减轻中枢神经系统(CNS)炎症,尤其是巨噬细胞和CD4 T细胞的炎症。这些结果表明,血吸虫病可能通过下调促炎细胞因子的产生和改变CNS炎症来负向调节EAE的发病。