Lactobacillus-derived extracellular vesicles enhance host immune responses against vancomycin-resistant enterococci.
Lactobacillus-derived extracellular vesicles enhance host immune responses against vancomycin-resistant enterococci.
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DOI：
10.1186/s12866-017-0977-7
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发表时间：
2017-03-14
期刊：
影响因子：
4.2
通讯作者：
Ramratnam B
中科院分区：
文献类型：
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作者：
Li M;Lee K;Hsu M;Nau G;Mylonakis E;Ramratnam B
众所周知，益生菌可以调节宿主对各种病原体的免疫反应。最近，细胞外囊泡（EVs）已成为宿主-病原体相互作用的潜在重要介质。在这项研究中，我们利用秀丽隐杆线虫和人类细胞，探讨了植物乳杆菌衍生的ev在调节宿主对万古霉素耐药屎肠球菌（VRE）反应中的作用。我们之前的工作表明，益生菌调节秀丽隐杆线虫与嗜酸乳杆菌NCFM延长了暴露于VRE的线虫的存活。同样，植物乳杆菌WCFS1衍生的细胞外囊泡（LDEVs）也能显著保护线虫免受VRE感染。为了分析这种ev诱导的保护作用的分子机制，我们发现用ldev处理秀丽隐杆线虫显著增加宿主防御基因cpr-1和ecc -60的转录。先前有报道称，cpr-1和ecc -60对细菌感染具有保护作用。用荧光染料标记的LDEVs培养人结肠源性Caco-2细胞，证实LDEVs可以转运到哺乳动物细胞中。此外，LDEV的摄取与CTSB（一种人类与cpr-1同源的基因）和REG3G（一种与ecc -60功能相似的人类基因）的显著上调有关。我们发现植物乳杆菌WCFS1产生的EVs上调宿主防御基因的表达，对宿主具有保护作用。利用益生菌衍生的电动汽车代替益生菌本身，为治疗VRE等耐药病原体提供了新的方向。本文的在线版本（doi:10.1186/s12866-017-0977-7）包含补充材料，可供授权用户使用。
Probiotic bacteria are known to modulate host immune responses against various pathogens. Recently, extracellular vesicles (EVs) have emerged as potentially important mediators of host-pathogen interactions. In this study, we explored the role of L. plantarum derived EVs in modulating host responses to vancomycin-resistant Enterococcus faecium (VRE) using both Caenorhabditis elegans and human cells. Our previous work has shown that probiotic conditioning C. elegans with L. acidophilus NCFM prolongs the survival of nematodes exposed to VRE. Similarly, L. plantarum WCFS1 derived extracellular vesicles (LDEVs) also significantly protected the worms against VRE infection. To dissect the molecular mechanisms of this EV-induced protection, we found that treatment of C. elegans with LDEVs significantly increased the transcription of host defense genes, cpr-1 and clec-60. Both cpr-1 and clec-60 have been previously reported to have protective roles against bacterial infections. Incubating human colon-derived Caco-2 cells with fluorescent dye-labeled LDEVs confirmed that LDEVs could be transported into the mammalian cells. Furthermore, LDEV uptake was associated with significant upregulation of CTSB, a human homologous gene of cpr-1, and REG3G, a human gene that has similar functions to clec-60. We have found that EVs produced from L. plantarum WCFS1 up-regulate the expression of host defense genes and provide protective effects on hosts. Using probiotic-derived EVs instead of probiotic bacteria themselves, this study provides a new direction to treat antimicrobial resistant pathogens, such as VRE. The online version of this article (doi:10.1186/s12866-017-0977-7) contains supplementary material, which is available to authorized users.