Parthasarathy G, Mansfield L S
Department of Microbiology and Molecular Genetics, B43 Food Safety Building, Michigan State University, East Lansing, MI-48824, USA.
Vet Parasitol. 2005 Aug 10;131(3-4):317-24. doi: 10.1016/j.vetpar.2005.03.043.
Immune responses to gastrointestinal helminth infections have received increasing attention due to similarities to allergen-induced responses. In fact, the whipworm parasite of swine, Trichuris suis, has been used in beginning clinical trials as an antidote to inflammatory bowel disease. This strategy was based on this similarity and the recognition that other worms have been documented to induce anti-inflammatory responses in the host. In an effort to understand the basis for this response, we hypothesized that the proteins and peptides secreted by T. suis stimulate local intestinal epithelial cells to produce anti-inflammatory cytokines. To test this hypothesis in a correlate system of the natural swine host, T. suis excretory secretory products (ESP) were used to treat both differentiated and undifferentiated intestinal pig epithelial cells (IPEC-1) in vitro as a model for the effect on villus tip and crypt epithelial cells in the vicinity of the worms. IPEC-1 were exposed to low-level doses (0.3mg/ml) of T. suis ESP, and IL-4, IL-6 and IL-10 cytokine responses were measured by an enzyme-linked immunosorbant assay (ELISA). IL-6 was the predominant cytokine produced, accompanied by moderate IL-10 secretion from both differentiated and undifferentiated cells. As expected, IL-4 was not produced by IPEC-1. Additionally, IL-6 and IL-10 cytokines were produced within 24h, suggesting that these two cytokines form part of the primary host response to T. suis infections. These data suggest that T. suis ESP could enhance host immune responses and modulation through the induction of enteric IL-6 and IL-10.
由于与过敏原诱导的反应相似，对胃肠道蠕虫感染的免疫反应受到了越来越多的关注。事实上，猪的鞭虫寄生虫猪鞭虫已被用于炎症性肠病的初步临床试验。这一策略基于这种相似性以及其他蠕虫已被证明能在宿主体内诱导抗炎反应的认识。为了理解这种反应的基础，我们假设猪鞭虫分泌的蛋白质和肽刺激局部肠上皮细胞产生抗炎细胞因子。为了在天然猪宿主的相关系统中验证这一假设，猪鞭虫排泄分泌产物（ESP）被用于体外处理分化和未分化的猪肠上皮细胞（IPEC-1），以此作为对蠕虫附近绒毛顶端和隐窝上皮细胞影响的模型。将IPEC-1暴露于低剂量（0.3mg/ml）的猪鞭虫ESP中，通过酶联免疫吸附测定（ELISA）测量IL-4、IL-6和IL-10细胞因子的反应。IL-6是产生的主要细胞因子，分化和未分化细胞均伴有适度的IL-10分泌。正如预期的那样，IPEC-1不产生IL-4。此外，IL-6和IL-10细胞因子在24小时内产生，表明这两种细胞因子是宿主对猪鞭虫感染的主要反应的一部分。这些数据表明，猪鞭虫ESP可以通过诱导肠道IL-6和IL-10来增强宿主免疫反应和调节作用。
