Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht Str. 74, 20359 Hamburg, Germany.
Exp Parasitol. 2012 Sep;132(1):69-75. doi: 10.1016/j.exppara.2011.06.001. Epub 2011 Jun 23.
It is estimated that over one third of the world population is infected with helminths, Strongyloides ssp. accounting for approximately 30-100 million cases. As helminth infections often result in a modulation of the host's immune system, infected people may display impaired responses to concurrent infections and to third party antigens. Here, we employ the experimental system of murine Strongyloides ratti infection to investigate the impact of helminth infections on experimental vaccinations. We demonstrate that concurrent infection with S. ratti strongly affected the humoral response to a thymus dependent model antigen, whereby predominantly Th1 associated IgG2b production was suppressed. We provide evidence that this suppression was due to modulation of T helper cell and not B cell function as the responses to a thymus independent model antigen remained unchanged in S. ratti infected mice. Moreover, using an adoptive transfer system, we show that infection with S. ratti directly interfered with antigen-specific proliferation of T cell receptor transgenic CD4(+) T helper cells in vivo. Finally, using IL-10 deficient mice and mice that selectively lack T helper cell derived IL-10 we rule out a role for host-derived IL-10 in mediating the suppression of thymus dependent model antigen response in S. ratti infected mice.
据估计，全世界有超过三分之一的人口感染了蠕虫，其中大约有 3000 万至 1 亿例是 Strongyloides ssp. 感染。由于蠕虫感染通常会导致宿主免疫系统的调节，受感染的人可能对同时发生的感染和第三方抗原的反应受损。在这里，我们采用实验性的鼠 Strongyloides ratti 感染系统来研究蠕虫感染对实验性疫苗接种的影响。我们证明，同时感染 S. ratti 强烈影响了对胸腺依赖性模型抗原的体液反应，主要是 Th1 相关 IgG2b 的产生受到抑制。我们提供的证据表明，这种抑制是由于辅助性 T 细胞的调节，而不是 B 细胞功能的调节，因为 S. ratti 感染小鼠对胸腺非依赖性模型抗原的反应没有改变。此外，我们通过过继转移系统显示，S. ratti 的感染直接干扰了体内抗原特异性 TCR 转基因 CD4(+)辅助性 T 细胞的增殖。最后，我们使用 IL-10 缺陷小鼠和选择性缺乏辅助性 T 细胞衍生的 IL-10 的小鼠，排除了宿主来源的 IL-10 在介导 S. ratti 感染小鼠中对胸腺依赖性模型抗原反应的抑制中的作用。
