Menge C, Wieler L H, Schlapp T, Baljer G
Institut für Hygiene und Infektionskrankheiten der Tiere der Justus-Liebig-Universität, Giessen, D-35392 Giessen, Germany.
Infect Immun. 1999 May;67(5):2209-17. doi: 10.1128/IAI.67.5.2209-2217.1999.
Shiga toxin-producing Escherichia coli (STEC) is widespread in the cattle population, but the clinical significance of Shiga toxins (Stx's) for the bovine species remains obscure. Since Stx's exert immunomodulating effects in other species, we examined the effect of purified Stx1 on a bovine B lymphoma cell line (BL-3) and peripheral blood mononuclear cells (PBMC) isolated from adult bovine blood by viability assays and flow cytometry analysis. Stx1 markedly induced apoptosis in stimulated BL-3 cells. The susceptibility of this B-cell-derived cell line was induced only by either lipopolysaccharide (LPS) or pokeweed mitogen, while cultures stimulated with T-cell mitogens were unaffected by the toxin. In contrast, Stx1 did not induce cellular death-neither apoptosis nor necrosis-in primary cultures of PBMC but hindered the mitogen-induced increase in metabolic activity. The influence of Stx1 on single PBMC subpopulations varied with the type of mitogenic stimulus applied. Stimulation with phytohemagglutinin P particularly induced the proliferation of bovine CD8-expressing (BoCD8(+)) cells, and this proliferative response was blocked by Stx1. On the other hand, Stx1 reduced the portion of viable B cells in the presence of LPS. Modulation of activation marker expression (BoCD25 and BoCD71) by Stx1 indicated that the toxin hindered the proliferation of cells by blocking their activation. In conclusion, we assume that Stx1 contributes to the pathogenesis of STEC-associated diarrhea in calves by suppressing the mucosa-associated immune response. The usefulness of cattle as a model in which to study Stx-induced immunomodulation is discussed.
产志贺毒素大肠杆菌（STEC）在牛群中广泛存在，但志贺毒素（Stx's）对牛类的临床意义仍不清楚。由于Stx's在其他物种中发挥免疫调节作用，我们通过活力测定和流式细胞术分析，研究了纯化的Stx1对从成年牛血液中分离的牛B淋巴瘤细胞系（BL-3）和外周血单个核细胞（PBMC）的影响。Stx1显著诱导刺激后的BL-3细胞凋亡。这种B细胞来源的细胞系仅对脂多糖（LPS）或商陆有丝分裂原敏感，而用T细胞有丝分裂原刺激的培养物不受该毒素影响。相反，Stx1在PBMC原代培养物中既不诱导细胞死亡（凋亡或坏死），但会阻碍有丝分裂原诱导的代谢活性增加。Stx1对单个PBMC亚群的影响因所应用的有丝分裂原刺激类型而异。用植物血凝素P刺激特别诱导表达牛CD8（BoCD8(+)）细胞的增殖，而这种增殖反应被Stx1阻断。另一方面，在LPS存在的情况下，Stx1减少了存活B细胞的比例。Stx1对激活标志物表达（BoCD25和BoCD71）的调节表明，该毒素通过阻断细胞激活来阻碍其增殖。总之，我们认为Stx1通过抑制黏膜相关免疫反应，在犊牛STEC相关性腹泻的发病机制中起作用。本文还讨论了牛作为研究Stx诱导免疫调节的模型的实用性。
