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首页> 外文期刊>Infection and immunity >Enterotoxin-Based Mucosal Adjuvants Alter Antigen Trafficking and Induce Inflammatory Responses in the Nasal Tract
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Enterotoxin-Based Mucosal Adjuvants Alter Antigen Trafficking and Induce Inflammatory Responses in the Nasal Tract

机译：基于肠毒素的粘膜佐剂可改变抗原运输并诱导鼻道炎症反应。

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The safety of nasal vaccines containing enterotoxin-based mucosal adjuvants has not been studied in detail. Previous studies have indicated that native cholera toxin (nCT) can alter antigen trafficking when applied nasally. In this study, we determined the enterotoxin-based variables that alter antigen trafficking. To measure the influence of enterotoxin-based mucosal adjuvants on antigen trafficking in the nasal tract, native and mutant enterotoxins were coadministered with radiolabeled tetanus toxoid (TT). The nCT and heat-labile enterotoxin type 1 (LTh-1) redirected TT into the olfactory neuroepithelium (ON/E). Antigen redirection occurred mainly across the nasal epithelium without subsequent transport along olfactory neurons into the olfactory bulbs (OB). Thus, no significant accumulation of the vaccine antigen TT was observed in the OB when coadministered with nCT. In contrast, neither mutant CT nor mutant LTh-1, which lack ADP-ribosyltransferase activity, redirected TT antigen into the ON/E. Thus, ADP-ribosyltransferase activity was essential for antigen trafficking across the olfactory epithelium. Accumulation of TT in the ON/E was also due to B-subunit binding to GM1 gangliosides, as was demonstrated (i) by redirection of TT by LTh-1 in a dose-dependent manner, (ii) by ganglioside inhibition of the antigen redirection by LTh-1 and nCT, and (iii) by the use of LT-IIb, a toxin that binds to gangliosides other than GM1. Redirection of TT into the ON/E coincided with elevated production of interleukin 6 (IL-6) but not IL-1β or tumor necrosis factor alpha in the nasal mucosa. Thus, redirection of TT is dependent on ADP-ribosyltransferase activity and GM1 binding and is associated with production of the inflammatory cytokine IL-6.
机译：尚未详细研究含有基于肠毒素的粘膜佐剂的鼻疫苗的安全性。先前的研究表明，鼻内霍乱毒素（nCT）可以改变抗原运输。在这项研究中，我们确定了改变抗原运输的基于肠毒素的变量。为了测量基于肠毒素的粘膜佐剂对鼻道抗原运输的影响，将天然和突变型肠毒素与放射性标记的破伤风类毒素（TT）共同使用。 nCT和1型不耐热肠毒素（LTh-1）将TT重定向到嗅觉神经上皮（ON / E）。抗原重定向主要发生在整个鼻上皮，而没有随后沿嗅神经元转运到嗅球（OB）中。因此，当与nCT共同施用时，在OB中未观察到疫苗抗原TT的显着积累。相反，缺乏ADP-核糖基转移酶活性的突变体CT和突变体LTh-1都没有将TT抗原重新定向到ON / E。因此，ADP-核糖基转移酶活性对于跨嗅上皮的抗原运输是必不可少的。在ON / E中TT的积累也归因于B​​亚基与GM1神经节苷脂的结合，如（i）LTh-1以剂量依赖性方式重定向TT，（ii）神经节苷脂抑制抗原所证明的那样通过LTh-1和nCT进行重定向，以及（iii）通过使用LT-IIb（一种与GM1以外的神经节苷脂结合的毒素）进行重定向。 TT重定向至ON / E与鼻黏膜中白介素6（IL-6）的产生升高，但IL-1β或肿瘤坏死因子α升高无关。因此，TT的重定向依赖于ADP-核糖基转移酶活性和GM1结合，并与炎性细胞因子IL-6的产生有关。

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