Abstract

Defensins are antimicrobial peptides that contribute broadly to innate immunity, including protection of mucosal tissues. Human α-defensin (HD) 6 is highly expressed by secretory Paneth cells of the small intestine. However, in contrast to the other defensins, it lacks appreciable bactericidal activity. Nevertheless, we report here that HD6 affords protection against invasion by enteric bacterial pathogens in vitro and in vivo. After stochastic binding to bacterial surface proteins, HD6 undergoes ordered self-assembly to form fibrils and nanonets that surround and entangle bacteria. This self-assembly mechanism occurs in vivo, requires histidine-27, and is consistent with x-ray crystallography data. These findings support a key role for HD6 in protecting the small intestine against invasion by diverse enteric pathogens and may explain the conservation of HD6 throughout Hominidae evolution.

Links

Publisher Full Text

Authors

Chu H, Pazgier M, Jung G, Nuccio SP, Castillo PA, de Jong MF, Winter MG, Winter SE, Wehkamp J, Shen B, Salzman NH, Underwood MA, Tsolis RM, Young GM, Lu W, Lehrer RI, Bäumler AJ, Bevins CL

Institution

Department of Microbiology and Immunology, School of Medicine, University of California, Davis, CA 95616, USA.

Source

Science (New York, N.Y.) 337:6093 2012 Jul 27 pg 477-81

MeSH

Adhesins, Bacterial
Animals
Bacterial Proteins
Cell Line
Humans
Immunity, Innate
Immunity, Mucosal
Intestinal Mucosa
Intestine, Small
Macromolecular Substances
Mice
Mice, Transgenic
Microscopy, Electron, Scanning
Models, Molecular
Nanostructures
Paneth Cells
Peptides
Protein Binding
Protein Multimerization
Protein Structure, Quaternary
Salmonella Infections, Animal
Salmonella typhimurium
Yersinia enterocolitica
alpha-Defensins
env Gene Products, Human Immunodeficiency Virus

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22722251