Genomic analysis of immune response against Vibrio cholerae hemolysin in Caenorhabditis elegans.
Genomic analysis of immune response against Vibrio cholerae hemolysin in Caenorhabditis elegans.
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DOI：
10.1371/journal.pone.0038200
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Cinar HN
中科院分区：
文献类型：
--
作者：
Sahu SN;Lewis J;Patel I;Bozdag S;Lee JH;LeClerc JE;Cinar HN
霍乱弧菌溶细胞素 (VCC) 是可能导致人类疾病发病机制的霍乱弧菌辅助毒力因子之一。 VCC由hlyA基因编码，属于最常见的一类细菌毒素，称为成孔毒素（PFT）。霍乱弧菌通过不依赖霍乱毒素的方式感染并杀死秀丽隐杆线虫。 VCC 是感染过程中致死、生长迟缓和肠细胞空泡化所必需的。 However, little is known about the host gene expression responses against VCC.为了解决这个问题，我们对暴露于具有完整和缺失 hlyA 基因的霍乱弧菌菌株的线虫进行了微阵列研究。许多已鉴定的 VCC 调节基因，包括 C 型凝集素、类朊病毒（富含谷氨酰胺 [Q]/天冬酰胺 [N]）结构域基因、受胰岛素/IGF-1 介导的信号传导 (IIS) 途径调节的基因，之前被报道为线虫中针对其他细菌的先天免疫反应的介质。使用 RNAi 证实了 VCC 上调基因子集的保护功能。通过名为 FastMEDUSA 的机器学习算法，我们鉴定了几种假定的 VCC 诱导的免疫调节转录因子和转录因子结合基序。我们的结果表明，VCC 是一种主要毒力因子，在线虫感染霍乱弧菌期间，它会诱导多种免疫反应相关基因。
Vibrio cholerae cytolysin (VCC) is among the accessory V. cholerae virulence factors that may contribute to disease pathogenesis in humans. VCC, encoded by hlyA gene, belongs to the most common class of bacterial toxins, known as pore-forming toxins (PFTs). V. cholerae infects and kills Caenorhabditis elegans via cholerae toxin independent manner. VCC is required for the lethality, growth retardation and intestinal cell vacuolation during the infection. However, little is known about the host gene expression responses against VCC. To address this question we performed a microarray study in C. elegans exposed to V. cholerae strains with intact and deleted hlyA genes. Many of the VCC regulated genes identified, including C-type lectins, Prion-like (glutamine [Q]/asparagine [N]-rich)-domain containing genes, genes regulated by insulin/IGF-1-mediated signaling (IIS) pathway, were previously reported as mediators of innate immune response against other bacteria in C. elegans. Protective function of the subset of the genes up-regulated by VCC was confirmed using RNAi. By means of a machine learning algorithm called FastMEDUSA, we identified several putative VCC induced immune regulatory transcriptional factors and transcription factor binding motifs. Our results suggest that VCC is a major virulence factor, which induces a wide variety of immune response- related genes during V. cholerae infection in C. elegans.
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