Human Enteric α-Defensin 5 Promotes Shigella Infection by Enhancing Bacterial Adhesion and Invasion

Dan Xu, Chongbing Liao, Bing Zhang, W. David Tolbert, Wangxiao He, Zhijun Dai, Wei Zhang, Weirong Yuan, Marzena Pazgier, Jiankang Liu, Jun Yu, Philippe J. Sansonetti, Charles L Bevins, Yongping Shao, Wuyuan Lu

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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. How Shigella can be infectious in humans despite lacking clear mechanisms for mucosal adhesion remains a long-standing enigma concerning its pathogenesis. Xu et al. demonstrate that Shigella exploits the host defense peptide HD5 in the gut to attain its ability to colonize and destroy the intestinal epithelium.

Original languageEnglish (US)
Pages (from-to)1233-1244.e7
JournalImmunity
Volume48
Issue number6
DOIs
StatePublished - Jun 19 2018

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Keywords

  • antimicrobial peptide
  • bacterial adhesion
  • defensin
  • enteropathogenic bacteria
  • epithelial integrity
  • host-microbe interaction
  • innate immunity
  • Shigella

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Xu, D., Liao, C., Zhang, B., Tolbert, W. D., He, W., Dai, Z., Zhang, W., Yuan, W., Pazgier, M., Liu, J., Yu, J., Sansonetti, P. J., Bevins, C. L., Shao, Y., & Lu, W. (2018). Human Enteric α-Defensin 5 Promotes Shigella Infection by Enhancing Bacterial Adhesion and Invasion. Immunity, 48(6), 1233-1244.e7. https://doi.org/10.1016/j.immuni.2018.04.014