D'Elia R, Else K J
University of Manchester, UK. riccardo.d'
Parasite Immunol. 2009 Mar;31(3):123-31. doi: 10.1111/j.1365-3024.2008.01088.x.
Trichuris muris, the mouse whipworm, is used as a laboratory model of the human parasite T. trichiura. Three laboratory isolates of T. muris exist - the E, J and S isolates. Previous data have shown that the S isolate survives to chronicity in C57BL/6 mice unlike the E and J isolates, which are expelled. The ability of the S isolate to persist is thought to be due to it secreting unique excretory/secretory antigens, which interact with APCs such that protective T cell responses do not develop. To determine whether APCs respond differently to E/S antigens from the three isolates we cultured isolate-specific E/S with bone marrow-derived macrophages (BMMPhi) and dendritic cells (BMDCs) in vitro. Markers of co-stimulation and levels of MHC-II were analysed by FACS and cytokine levels in supernatants quantified. E/S antigens from the S isolate consistently stimulated significantly higher levels of IL-10 and IL-6 from both macrophages (F4/80(+)CD11b(+)CD11c(-)) and dendritic cells (CD11c(+)CD11b(+)F4/80(-)) compared to J and E isolate E/S. If these in vitro differences in APC-derived cytokines, particularly IL-10, are biologically significant in vivo, they may contribute to the S isolate survival, by creating a regulatory cytokine environment in which protective immune responses are less effective.
小鼠鞭虫毛首鞭形线虫（Trichuris muris）被用作人类寄生虫毛首鞭形线虫（T. trichiura）的实验室模型。毛首鞭形线虫存在三种实验室分离株——E、J和S分离株。先前的数据表明，与被排出的E和J分离株不同，S分离株在C57BL/6小鼠中可存活至慢性期。S分离株持续存在的能力被认为是由于它分泌独特的排泄/分泌抗原，这些抗原与抗原呈递细胞（APC）相互作用，从而不会产生保护性T细胞反应。为了确定APC对来自这三种分离株的排泄/分泌（E/S）抗原的反应是否不同，我们在体外将分离株特异性的E/S与骨髓来源的巨噬细胞（BMMPhi）和树突状细胞（BMDC）进行培养。通过荧光激活细胞分选术（FACS）分析共刺激标志物和MHC-II水平，并对上清液中的细胞因子水平进行定量。与J和E分离株的E/S相比，S分离株的E/S抗原持续刺激巨噬细胞（F4/80(+)CD11b(+)CD11c(-)）和树突状细胞（CD11c(+)CD11b(+)F4/80(-)）产生显著更高水平的IL-10和IL-6。如果APC衍生的细胞因子，特别是IL-10，在体外的这些差异在体内具有生物学意义，它们可能通过创造一种调节性细胞因子环境来促进S分离株的存活，在这种环境中保护性免疫反应的效果较差。
