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Updated: Jan 5, 2026
Author Spotlight: Advancements in Understanding and Combatting Shigella Infections
Published on: February 9, 2024
Human Enteric Defensin 5 Promotes Shigella Infection of Macrophages
Dan Xu1,2, Chongbing Liao2,3, Jiu Xiao4
1Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China dan.xu@xjtu.edu.cn wlu@ihv.umaryland.edu.
Abstract:
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 Shigella in breaching the intestinal epithelium in vitro and in vivo Whether and how HD5 influences Shigella infection of resident macrophages following its invasion of the intestinal epithelium remain poorly understood. Here, we report that HD5 greatly promoted phagocytosis of Shigella by macrophages by targeting the bacteria to enhance bacterium-to-cell contacts in a structure- and sequence-dependent fashion. Subsequent intracellular multiplication of phagocytosed Shigella led to massive necrotic cell death and release of the bacteria. HD5-promoted phagocytosis of Shigella was independent of the status of the type 3 secretion system. Furthermore, HD5 neither inhibited nor enhanced phagosomal escape of Shigella Collectively, these findings confirm a potential pathogenic role of HD5 in Shigella infection of not only epithelial cells but also macrophages, illuminating how an enteropathogen exploits a host protective factor for virulence and infection.
Insights
Human enteric α-defensin 5 (HD5) enhances Shigella uptake by macrophages, promoting bacterial growth and cell death. This suggests HD5 may play a pathogenic role in Shigella infections.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Human α-defensins are antimicrobial peptides crucial for innate immunity.
- Human enteric α-defensin 5 (HD5) is vital for intestinal homeostasis.
- HD5 facilitates Shigella breaching of the intestinal epithelium.
Purpose of the Study:
- To investigate the role of HD5 in Shigella infection of macrophages.
- To elucidate the mechanisms by which HD5 influences Shigella-macrophage interactions.
Main Methods:
- Macrophage phagocytosis assays with Shigella in the presence of HD5.
- Analysis of Shigella intracellular survival and host cell death.
- Assessment of HD5's effect on Shigella's type 3 secretion system and phagosomal escape.
Main Results:
- HD5 significantly promoted Shigella phagocytosis by macrophages via enhanced bacterium-to-cell contacts.
- HD5-promoted phagocytosis led to increased intracellular Shigella multiplication, necrotic cell death, and bacterial release.
- HD5's effect on phagocytosis was independent of the type 3 secretion system and did not affect phagosomal escape.
Conclusions:
- HD5 plays a pathogenic role in Shigella infection, extending beyond epithelial cells to macrophages.
- Shigella exploits the host protective factor HD5 for its virulence and infection progression.
- HD5 promotes Shigella virulence by enhancing macrophage uptake and subsequent host cell lysis.
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