Menge Christian, Blessenohl Maike, Eisenberg Tobias, Stamm Ivonne, Baljer Georg
Institut für Hygiene und Infektionskrankheiten der Tiere der Justus-Liebig-Universität Giessen, D-35392 Giessen, Germany.
Infect Immun. 2004 Apr;72(4):1896-905. doi: 10.1128/IAI.72.4.1896-1905.2004.
The discovery that bovine peripheral lymphocytes are sensitive to Stx1 identified a possible mechanism for the persistence of infections with Shiga toxin (Stx)-producing Escherichia coli (STEC) in the bovine reservoir host. If intraepithelial lymphocytes (IEL) are also sensitive to Stx1, the idea that Stx1 affects inflammation in the bovine intestine is highly attractive. To prove this hypothesis, ileal IEL (iIEL) were prepared from adult cattle, characterized by flow cytometry, and subjected to functional assays in the presence and absence of purified Stx1. We found that 14.9% of all iIEL expressed Gb(3)/CD77, the Stx1 receptor on bovine lymphocytes, and 7.9% were able to bind the recombinant B subunit of Stx1. The majority of Gb(3)/CD77(+) cells were activated CD3(+) CD6(+) CD8 alpha(+) T cells, whereas only some CD4(+) T cells and B cells expressed Gb(3)/CD77. However, Stx1 blocked the mitogen-induced transformation to enlarged blast cells within all subpopulations to a similar extent and significantly reduced the percentage of Gb(3)/CD77(+) cells. Although Stx1 did not affect the natural killer cell activity of iIEL, the toxin accelerated the synthesis of interleukin-4 (IL-4) mRNA and reduced the amount of IL-8 mRNA in bovine iIEL cultures. Because the intestinal system comprises a rich network of interactions between different types of cells and any dysfunction may influence the course of intestinal infections, this demonstration that Stx1 can target bovine IEL may be highly relevant for our understanding of the interplay between STEC and its reservoir host.
牛外周淋巴细胞对志贺毒素1（Stx1）敏感这一发现，为产志贺毒素（Stx）的大肠杆菌（STEC）在牛储存宿主中持续感染提供了一种可能的机制。如果上皮内淋巴细胞（IEL）也对Stx1敏感，那么Stx1影响牛肠道炎症的观点就极具吸引力。为了验证这一假设，从成年牛制备回肠IEL（iIEL），通过流式细胞术进行表征，并在有和没有纯化的Stx1的情况下进行功能测定。我们发现，所有iIEL中有14.9%表达Gb(3)/CD77，即牛淋巴细胞上的Stx1受体，7.9%能够结合重组Stx1 B亚基。大多数Gb(3)/CD77(+)细胞是活化的CD3(+) CD6(+) CD8α(+) T细胞，而只有一些CD4(+) T细胞和B细胞表达Gb(3)/CD77。然而，Stx1在所有亚群中以相似程度阻断了丝裂原诱导的向增大的母细胞的转化，并显著降低了Gb(3)/CD77(+)细胞的百分比。虽然Stx1不影响iIEL的自然杀伤细胞活性，但该毒素加速了牛iIEL培养物中白细胞介素-4（IL-4）mRNA的合成并减少了IL-8 mRNA的量。由于肠道系统包含不同类型细胞之间丰富的相互作用网络，任何功能障碍都可能影响肠道感染的进程，因此Stx1可靶向牛IEL这一证明对于我们理解STEC与其储存宿主之间的相互作用可能高度相关。
