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首页> 外文期刊>Infection and immunity >An Enzymatically Active A Domain Is Required for Cholera-Like Enterotoxins To Induce a Long-Lived Blockade on the Induction of Oral Tolerance: New Method for Screening Mucosal Adjuvants
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An Enzymatically Active A Domain Is Required for Cholera-Like Enterotoxins To Induce a Long-Lived Blockade on the Induction of Oral Tolerance: New Method for Screening Mucosal Adjuvants

机译：霍乱样肠毒素诱导对口服耐受性诱导的长期封锁需要酶活性A域：筛选粘膜佐剂的新方法

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The cholera-like enterotoxins (CLETS), cholera toxin (CT) and Escherichia coli heat-labile toxin (LT), are powerful mucosal adjuvants. Here we show that these toxins also induce a long-lived blockade (of at least 6 months) on the induction of oral tolerance when they are coadministered with the antigen ovalbumin. Strikingly, only enzymatically active CLETS induced this blockade on the induction of oral tolerance. In this regard, the enzymatically inactive mutants of CT and LT, CTK63 and LTK63, and their recombinant B pentamers, rCTB and rLTB, failed to block the induction of oral tolerance, demonstrating a stringent requirement for an enzymatically active A domain in this phenomenon. Together with the results of other recent studies, these results indicate that the enzymatic activity of CLETS, most likely cyclic AMP elevation, is responsible for their adjuvant effects. The results of this study also indicate that measuring the ability of putative mucosal adjuvants to block the induction of oral tolerance may be a superior method for measuring mucosal adjuvanticity.
机译：霍乱样肠毒素（CLETS），霍乱毒素（CT）和大肠杆菌不耐热毒素（LT）是强大的粘膜佐剂。在这里，我们显示当这些毒素与卵清蛋白抗原同时给药时，它们在诱导口服耐受性上也诱导了长效封锁（至少6个月）。令人惊讶的是，只有具有酶促活性的CLETS才能诱导这种对口服耐受性的诱导作用。在这方面，CT和LT，CTK63和LTK63的无酶突变体，以及它们的重组B五聚体rCTB和rLTB，不能阻止对口服耐受的诱导，这表明对该现象中酶活性A结构域的严格要求。与其他近期研究的结果一起，这些结果表明CLETS的酶促活性（最可能是环状AMP升高）是其佐剂作用的原因。这项研究的结果还表明，测量假定的粘膜佐剂阻断诱导口腔耐受的能力可能是测量粘膜佐剂性的一种较好方法。

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