Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, People's Republic of China.
Mol Cell Biochem. 2012 Jan;360(1-2):79-88. doi: 10.1007/s11010-011-1046-4. Epub 2011 Sep 11.
Trichinella spiralis is a zoonotic nematode and food borne parasite and infection with T. spiralis leads to suppression of the host immune response and other immunopathologies. The excretory/secretory (ES) products of T. spiralis play important roles in the process of immunomodulation. However, the mechanisms and related molecules are unknown. Macrophages, a target for immunomodulation by the helminth parasite, play a critical role in initiating and modulating the host immune response to parasite infection. In this study, we examined the effect of ES products from different stages of T. spiralis on modulating J774A.1 macrophage activities. ES products from different stages of T. spiralis reduced the capacity of macrophages to express pro-inflammatory cytokines (tumor necrosis factor α, interleukin-1β , interleukin-6 , and interleukin-12) in response to lipopolysaccharide (LPS) challenge. However, only ES products from 3-day-old adult worms and 5-day-old adult worms/new-born larvae significantly inhibited inducible nitric oxide synthase gene expression in LPS-induced macrophages. In addition, ES products alone boosted the expression of anti-inflammatory cytokines interleukin-10 and transforming growth factor-β and effector molecule arginase 1 in J774A.1 macrophages. Signal transduction studies showed that ES products significantly inhibited nuclear factor-κB translocation into the nucleus and the phosphorylation of both extracellular signal-regulated protein kinase 1/2 and p38 mitogen-activated protein kinase in LPS-stimulated J774A.1 macrophages. These results suggest that ES products regulate host immune response at the macrophage level through inhibition of pro-inflammatory cytokines production and induction of macrophage toward the alternative phenotype, which maybe important for worm survival and host health.
旋毛虫是一种人畜共患的线虫和食源性寄生虫，感染旋毛虫会导致宿主免疫反应受到抑制和其他免疫病理。旋毛虫的排泄/分泌（ES）产物在免疫调节过程中发挥重要作用。然而，其机制和相关分子尚不清楚。 巨噬细胞是寄生虫免疫调节的靶标，在启动和调节宿主对寄生虫感染的免疫反应中起着关键作用。在这项研究中，我们研究了旋毛虫不同发育阶段的 ES 产物对 J774A.1 巨噬细胞活性的调节作用。旋毛虫不同发育阶段的 ES 产物降低了巨噬细胞在脂多糖（LPS）刺激下表达促炎细胞因子（肿瘤坏死因子 α、白细胞介素-1β、白细胞介素-6 和白细胞介素-12）的能力。然而，只有来自 3 日龄成虫和 5 日龄成虫/新生幼虫的 ES 产物能显著抑制 LPS 诱导的巨噬细胞中诱导型一氧化氮合酶基因的表达。此外，ES 产物本身能促进抗炎细胞因子白细胞介素-10 和转化生长因子-β以及效应分子精氨酸酶 1 在 J774A.1 巨噬细胞中的表达。信号转导研究表明，ES 产物能显著抑制 LPS 刺激的 J774A.1 巨噬细胞中核因子-κB 向核内易位和细胞外信号调节激酶 1/2 和 p38 丝裂原激活蛋白激酶的磷酸化。这些结果表明，ES 产物通过抑制促炎细胞因子的产生和诱导巨噬细胞向替代表型来调节宿主免疫反应，这对蠕虫的生存和宿主的健康可能很重要。
