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.

 

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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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