Cêtre C, Pierrot C, Cocude C, Lafitte S, Capron A, Capron M, Khalife J
Institut Pasteur de Lille, 59019 Lille Cedex, France.
Infect Immun. 1999 Jun;67(6):2713-9. doi: 10.1128/IAI.67.6.2713-2719.1999.
In contrast to most mouse strains, rats eliminate the primary schistosome burden around 4 weeks postinfection and subsequently develop protective immunity to reinfection. In rat schistosomiasis, we have shown predominant expression of a Th2-type cytokine response at the mRNA level after primary infection. In the present study, we showed a significant increase in interleukin-4 (IL-4) mRNA expression in inguinal lymph nodes early after a secondary infection. IL-5 mRNA expression showed a significant increase at days 2 and 4 postreinfection in the spleen and lymph nodes, respectively. We did not detect any gamma interferon (IFN-gamma) mRNA after a challenge infection. Analysis of cytokine secretion by stimulated spleen cells after a primary infection showed predominant expression of IL-4 with maximum production on day 21, accompanied by production of IL-5 from day 11 to day 67. A significant increase in IFN-gamma secretion was detected at day 21. Analysis of immunoglobulin G2b (IgG2b) and IgG2c (Th1-related isotypes) showed undetectable levels of IgG2b, but detectable levels of specific IgG2c antibodies were observed from day 42. The analysis of Th2-related isotypes showed high specific IgG1 and IgG2a antibody titers from day 29. After a secondary infection, only IL-4 and IL-5 secretion was sustained. This is supported by the increased production of Th2-related isotypes. These findings showed that S. mansoni infection can drive Th2 responses in rats in the absence of egg production which is required to induce a Th2 response in mice and are in favor of the role of Th2-type cytokines in protective immunity against reinfection.
与大多数小鼠品系不同,大鼠在感染后约4周消除主要的血吸虫负荷,并随后产生对再感染的保护性免疫。在大鼠血吸虫病中,我们已表明初次感染后在mRNA水平上主要表达Th2型细胞因子反应。在本研究中,我们显示再次感染后早期腹股沟淋巴结中白细胞介素-4(IL-4)mRNA表达显著增加。IL-5 mRNA表达在再次感染后第2天和第4天分别在脾脏和淋巴结中显著增加。攻击感染后我们未检测到任何γ干扰素(IFN-γ)mRNA。对初次感染后刺激的脾细胞的细胞因子分泌分析显示,IL-4主要表达,在第21天产量最高,从第11天到第67天伴有IL-5产生。在第21天检测到IFN-γ分泌显著增加。对免疫球蛋白G2b(IgG2b)和IgG2c(Th1相关同种型)的分析显示未检测到IgG2b水平,但从第42天观察到可检测水平的特异性IgG2c抗体。对Th2相关同种型的分析显示从第29天起特异性IgG1和IgG2a抗体滴度很高。再次感染后,仅IL-4和IL-5分泌持续存在。这得到Th2相关同种型产量增加的支持。这些发现表明,曼氏血吸虫感染可在大鼠中驱动Th2反应,而无需产生虫卵,而产生虫卵是在小鼠中诱导Th2反应所必需 的,这支持了Th2型细胞因子在抗再感染保护性免疫中的作用。