Human alpha Defensin 6 Promotes Mucosal Innate Immunity Through Self–Assembled Peptide Nanonets

Papers of the Month: August, 2012


Human α-Defensin 6 Promotes Mucosal Innate Immunity Through Self-Assembled Peptide Nanonets

Science. 2012 Jul 27;337(6093):477-81. Epub 2012 Jun 21.

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


Click here to view article

Click here for Pubmed Abstract




Comments by Dr. Murray Gardner:

I chose this paper because it uses TG mice to establish the here-to-fore unknown function of a human defensin molecule (HD-6) present in Paneth cells of the small intestine. Moreover, the senior author, Charles Bevins,  is a friend and colleague at UCD and the editorial Perspective ( p 420), ,  is co-authored by Michael Selsted, another old friend, now Chair of the Pathology Dept at USC School of Medicine, my former home.


Human Paneth cells contain two alpha defensins, HD-5  and HD-6 which are active microbicides against diverse microbes and some viruses. As previously shown In TG mice, HD-5 has a direct microbicidal effect. To determine the function of CD-6 which lacks this activity,  the authors engineered the expression of HD-6 specifically in mouse Paneth cells, which lack an ortholog of HD-6. They  elegantly show that HD-6 anchors to bacterial appendages ( fimbria and flagella) and forms a peptide cobweb-like nanonet that protects against invasion of enteric bacterial pathogens in vitro and in vivo.


I have always wondered what the prominantly visible eosinophilic granules in the cytoplasm of Paneth cells were there for and it is indeed satisfying to now have the answer. A decreased secretion of HD-5 and HD-6 may predispose to Crohn’s Disease and other inflammatory bowel disease.



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