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首页> 外文期刊>Infection and immunity >Characterization of Receptor-Mediated Signal Transduction by Escherichia coli Type IIa Heat-Labile Enterotoxin in the Polarized Human Intestinal Cell Line T84
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Characterization of Receptor-Mediated Signal Transduction by Escherichia coli Type IIa Heat-Labile Enterotoxin in the Polarized Human Intestinal Cell Line T84

机译：大肠杆菌介导的IIa型对人类不稳定的肠道细胞系T84中的不耐热肠毒素的介导信号转导的表征

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Escherichia coli type IIa heat-labile enterotoxin (LTIIa) binds in vitro with highest affinity to ganglioside GD1b. It also binds in vitro with lower affinity to several other oligosialogangliosides and to ganglioside GM1, the functional receptor for cholera toxin (CT). In the present study, we characterized receptor-mediated signal transduction by LTIIa in the cultured T84 cell model of human intestinal epithelium. Wild-type LTIIa bound tightly to the apical surface of polarized T84 cell monolayers and elicited a Cl? secretory response. LTIIa activity, unlike CT activity, was not blocked by the B subunit of CT. Furthermore, an LTIIa variant with a T14I substitution in its B subunit, which binds in vitro to ganglioside GM1 but not to ganglioside GD1b, was unable to bind to intact T84 cells and did not elicit a Cl? secretory response. These findings show that ganglioside GM1 on T84 cells is not a functional receptor for LTIIa. The LTIIa receptor on T84 cells was inactivated by treatment with neuraminidase. Furthermore, LTIIa binding was blocked by tetanus toxin C fragment, which binds to gangliosides GD1b and GT1b. These findings support the hypothesis that ganglioside GD1b, or possibly a glycoconjugate with a GD1b-like oligosaccharide, is the functional receptor for LTIIa on T84 cells. The LTIIa-receptor complexes from T84 cells were associated with detergent-insoluble membrane microdomains (lipid rafts), extending the correlation between toxin binding to lipid rafts and toxin function that was previously established for CT. However, the extent of association with lipid rafts and the magnitude of the Cl? secretory response in T84 cells were less for LTIIa than for CT. These properties of LTIIa and the previous finding that enterotoxin LTIIb binds to T84 cells but does not associate with lipid rafts or elicit a Cl? secretory response may explain the low pathogenicity for humans of type II enterotoxin-producing isolates of E. coli.
机译：大肠杆菌IIa型不耐热肠毒素（LTIIa）在体外与神经节苷脂GD1b具有最高的亲和力。它还在体外以较低的亲和力与其他几种寡唾液酸神经节苷脂和神经节苷脂GM1（霍乱毒素（CT）的功能性受体）结合。在本研究中，我们在培养的人肠上皮T84细胞模型中表征了LTIIa介导的受体介导的信号转导。野生型LTIIa紧密结合到极化的T84细胞单层的顶端表面，并引发Cl ？分泌反应。与CT活性不同，LTIIa活性没有被CT的B亚基阻断。此外，在其B亚基中具有T14I取代的LTIIa变体在体外与神经节苷脂GM1结合，但与神经节苷脂GD1b不结合，不能与完整的T84细胞结合，也不会引起Cl ？分泌响应。这些发现表明，T84细胞上的神经节苷脂GM1不是LTIIa的功能性受体。通过用神经氨酸酶处理使T84细胞上的LTIIa受体失活。此外，LTIIa的结合被破伤风毒素C片段阻断，该片段与神经节苷脂GD1b和GT1b结合。这些发现支持以下假设：神经节苷脂GD1b或可能与GD1b样寡糖的糖缀合物是T84细胞上LTIIa的功能受体。来自T84细胞的LTIIa-受体复合物与去污剂不溶性膜微区（脂质筏）相关，从而扩展了毒素与脂质筏的结合与先前为CT建立的毒素功能之间的相关性。然而，与LT相比，LTIIa与T84细胞中脂筏的缔合程度和Cl ？分泌反应的幅度要小。 LTIIa的这些特性以及肠毒素LTIIb结合T84细胞但不与脂筏结合或引起Cl ？分泌反应的先前发现可能解释了II型产肠毒素分离株对人类的低致病性的 E。大肠杆菌。

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