Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK.
Vet Res. 2013 Aug 21;44(1):70. doi: 10.1186/1297-9716-44-70.
Teladorsagia circumcincta is an important pathogenic nematode of sheep. It has been demonstrated previously that stimulation of murine T lymphocytes with excretory-secretory (ES) products derived from fourth stage larvae of T. circumcincta (Tci-L4-ES) results in de novo expression of Foxp3, a transcription factor intimately involved in regulatory T cell function. In the current study, Foxp3⁺ T cell responses in the abomasum and the effects of Tci-L4-ES on ovine peripheral blood mononuclear cells (PBMC) following T. circumcincta infection were investigated. T. circumcincta infection resulted in a significant increase in numbers of abomasal Foxp3⁺ T cells, but not an increase in the proportion of T cells expressing Foxp3. Unlike in mice, Tci-L4-ES was incapable of inducing T cell Foxp3 expression but instead suppressed mitogen-induced and antigen-specific activation and proliferation of ovine PBMC in vitro. This effect was heat labile, suggesting that it is mediated by protein(s). Suppression was associated with up-regulation of interleukin-10 (IL-10) mRNA, and specific monoclonal antibody neutralisation of IL-10 resulted in a 50% reduction in suppression, indicating involvement of the IL-10 signaling pathway. Suppression was significantly reduced in PBMC isolated from T. circumcincta infected vs. helminth-naïve lambs, and this reduction in suppression was associated with an increase in Tci-L4-ES antigen-specific T cells within the PBMC. In conclusion, we have identified a mechanism by which T. circumcincta may modulate the host adaptive immune response, potentially assisting survival of the parasite within the host. However, the impact of Tci-L4-ES-mediated lymphocyte suppression during T. circumcincta infection remains to be determined.
贝氏环形泰勒虫是绵羊的一种重要致病性线虫。先前已经证明，用贝氏环形泰勒虫第四期幼虫（Tci-L4-ES）来源的排泄分泌产物刺激鼠 T 淋巴细胞，会导致 Foxp3 的从头表达，Foxp3 是一种与调节性 T 细胞功能密切相关的转录因子。在本研究中，研究了 Tci-L4-ES 在绵羊感染贝氏环形泰勒虫后对胃黏膜 Foxp3+T 细胞的影响以及对绵羊外周血单核细胞（PBMC）的影响。贝氏环形泰勒虫感染导致胃黏膜 Foxp3+T 细胞数量显著增加，但 T 细胞表达 Foxp3 的比例没有增加。与小鼠不同的是，Tci-L4-ES 不能诱导 T 细胞 Foxp3 表达，而是抑制体外绵羊 PBMC 有丝分裂原诱导和抗原特异性的激活和增殖。这种作用是热不稳定的，提示它是由蛋白质介导的。抑制作用与白细胞介素-10（IL-10）mRNA 的上调有关，特异性单克隆抗体中和 IL-10 导致抑制作用降低 50%，表明涉及 IL-10 信号通路。与未感染蠕虫的羔羊相比，从感染贝氏环形泰勒虫的羔羊分离的 PBMC 中的抑制作用显著降低，并且这种抑制作用的降低与 PBMC 中 Tci-L4-ES 抗原特异性 T 细胞的增加有关。总之，我们已经确定了贝氏环形泰勒虫可能调节宿主适应性免疫反应的机制，这可能有助于寄生虫在宿主中的生存。然而，Tci-L4-ES 介导的淋巴细胞抑制在贝氏环形泰勒虫感染期间的影响仍有待确定。
