Role of heat-stable enterotoxins in the induction of early immune responses in piglets after infection with enterotoxigenic Escherichia coli.

Role of heat-stable enterotoxins in the induction of early immune responses in piglets after infection with enterotoxigenic Escherichia coli.
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DOI:
10.1371/journal.pone.0041041
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Cox E
Cox E
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Loos M;Geens M;Schauvliege S;Gasthuys F;van der Meulen J;Dubreuil JD;Goddeeris BM;Niewold T;Cox E

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产生热稳定(ST)和/或热不稳定(LT)肠毒素的产肠毒素大肠杆菌(ETEC)菌株是仔猪断奶后腹泻的原因。然而,不同肠毒素在宿主针对 ETEC 感染的免疫反应中的相对重要性尚未明确。在本研究中,构建了 O149:F4ac+、LT+ STa+ STb+ ETEC 菌株的几种同基因突变菌株,这些菌株缺乏 LT 与一种或两种类型 ST 肠毒素(STa 和/或 STb)组合的表达。使用小肠段灌注 (SISP) 技术和微阵列分析来研究这些突变株在感染后 4 小时诱导的宿主早期免疫反应,并与野生型菌株和 PBS 对照进行比较。同时,感染后 4 小时测量猪小肠粘膜的净液体吸收量,使我们能够将肠毒素分泌与基因调控相关联。微阵列分析一方面显示非毒素相关的一般抗菌反应,包括PAP、MMP1和IL8等基因。另一方面,结果表明 STb 在断奶后感染后早期的小肠分泌中以及通过白细胞介素 1 和白细胞介素 17 等免疫介质的差异调节诱导的先天免疫反应中发挥主导作用。
Enterotoxigenic Escherichia coli (ETEC) strains that produce heat-stable (ST) and/or heat - labile (LT) enterotoxins are cause of post – weaning diarrhea in piglets. However, the relative importance of the different enterotoxins in host immune responses against ETEC infection has been poorly defined. In the present study, several isogenic mutant strains of an O149:F4ac+, LT+ STa+ STb+ ETEC strain were constructed that lack the expression of LT in combination with one or both types of ST enterotoxins (STa and/or STb). The small intestinal segment perfusion (SISP) technique and microarray analysis were used to study host early immune responses induced by these mutant strains 4 h after infection in comparison to the wild type strain and a PBS control. Simultaneously, net fluid absorption of pig small intestinal mucosa was measured 4 h after infection, allowing us to correlate enterotoxin secretion with gene regulation. Microarray analysis showed on the one hand a non-toxin related general antibacterial response comprising genes such as PAP, MMP1 and IL8. On the other hand, results suggest a dominant role for STb in small intestinal secretion early after post-weaning infection, as well as in the induced innate immune response through differential regulation of immune mediators like interleukin 1 and interleukin 17.
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