Human Enteric Defensin 5 Promotes Shigella Infection of Macrophages

• Published in: Infection and immunity 2019-12, Vol.88 (1)
• Main Authors: Xu, Dan, Liao, Chongbing, Xiao, Jiu, Fang, Kun, Zhang, Wei, Yuan, Weirong, Lu, Wuyuan
• Format: Article
• Language: English
• Subjects: alpha-Defensins - metabolism; Animals; Bacterial Adhesion; Cells, Cultured; Cellular Microbiology: Pathogen-Host Cell Molecular Interactions; Dysentery, Bacillary - microbiology; Dysentery, Bacillary - pathology; Epithelial Cells - microbiology; Host-Pathogen Interactions; Humans; Intestinal Mucosa - microbiology; Intestinal Mucosa - pathology; Macrophages - microbiology; Mice; Phagocytosis; Shigella - pathogenicity
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00769-19

Human α-defensins are 3- to 5-kDa disulfide-bridged peptides with a multitude of antimicrobial activities and immunomodulatory functions. Recent studies show that human enteric α-defensin 5 (HD5), a host defense peptide important for intestinal homeostasis and innate immunity, aids the highly infectious enteropathogen in breaching the intestinal epithelium and Whether and how HD5 influences infection of resident macrophages following its invasion of the intestinal epithelium remain poorly understood. Here, we report that HD5 greatly promoted phagocytosis of by macrophages by targeting the bacteria to enhance bacterium-to-cell contacts in a structure- and sequence-dependent fashion. Subsequent intracellular multiplication of phagocytosed led to massive necrotic cell death and release of the bacteria. HD5-promoted phagocytosis of was independent of the status of the type 3 secretion system. Furthermore, HD5 neither inhibited nor enhanced phagosomal escape of Collectively, these findings confirm a potential pathogenic role of HD5 in infection of not only epithelial cells but also macrophages, illuminating how an enteropathogen exploits a host protective factor for virulence and infection.