Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China; Center for Translational Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China; Institute of Human Virology and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA.
Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China; Center for Translational Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Immunity. 2018 Jun 19;48(6):1233-1244.e6. doi: 10.1016/j.immuni.2018.04.014. Epub 2018 May 29.
Shigella is a Gram-negative bacterium that causes bacillary dysentery worldwide. It invades the intestinal epithelium to elicit intense inflammation and tissue damage, yet the underlying mechanisms of its host selectivity and low infectious inoculum remain perplexing. Here, we report that Shigella co-opts human α-defensin 5 (HD5), a host defense peptide important for intestinal homeostasis and innate immunity, to enhance its adhesion to and invasion of mucosal tissues. HD5 promoted Shigella infection in vitro in a structure-dependent manner. Shigella, commonly devoid of an effective host-adhesion apparatus, preferentially targeted HD5 to augment its ability to colonize the intestinal epithelium through interactions with multiple bacterial membrane proteins. HD5 exacerbated infectivity and Shigella-induced pathology in a culture of human colorectal tissues and three animal models. Our findings illuminate how Shigella exploits innate immunity by turning HD5 into a virulence factor for infection, unveiling a mechanism of action for this highly proficient human pathogen.
志贺氏菌是一种革兰氏阴性细菌，可导致全球细菌性痢疾。它侵袭肠道上皮细胞，引发强烈的炎症和组织损伤，但宿主选择性和低感染剂量的潜在机制仍令人费解。在这里，我们报告志贺氏菌利用人类α-防御素 5（HD5），一种对肠道内稳态和先天免疫很重要的宿主防御肽，来增强其对粘膜组织的粘附和入侵能力。HD5 以结构依赖性方式促进了志贺氏菌在体外的感染。志贺氏菌通常缺乏有效的宿主粘附装置，通过与多种细菌膜蛋白相互作用，优先靶向 HD5 来增强其在肠道上皮定植的能力。HD5 在人结直肠组织培养物和三种动物模型中加重了感染性和志贺氏菌诱导的病理。我们的发现阐明了志贺氏菌如何通过将 HD5 转化为感染的毒力因子来利用先天免疫，揭示了这种高效的人类病原体的作用机制。
