Abstract
Enteric defensins likely play a key role in the management of the human microbiome throughout development. The functional and mechanistic diversity of defensins is much greater than was initially thought. Defensin expression and overall Paneth cell physiology likely plays a key role in the development of colitis and other inflammatory or dysbiotic diseases of the gut. As our understanding of enteric defensins grows, their potential as tools of clinical intervention becomes more apparent. In this review, we focus on the function and activity of Paneth Cell defensins and highlight their role in disease.
Highlights
The term “antimicrobial peptide” is used to describe a polypeptide chain of 5–100 residues that has broad-spectrum antimicrobial activity at one or more sites throughout the body (Bahar and Ren, 2013)
While there are over 5,000 distinct antimicrobial peptides described, they fall into three major categories: cathelicidins, defensins, and histatins, each having various domains and functions (Bahar and Ren, 2013; Zhao et al, 2013)
Much effort is being devoted to understanding the scope and functional importance of defensins, especially those involved in the maintenance of the gut epithelium as a barrier to enteric infection
Summary
The term “antimicrobial peptide” is used to describe a polypeptide chain of 5–100 residues that has broad-spectrum antimicrobial activity at one or more sites throughout the body (Bahar and Ren, 2013). With the rise of antimicrobial resistance, research into new antibiotic therapies is becoming increasingly important With this in mind, much effort is being devoted to understanding the scope and functional importance of defensins, especially those involved in the maintenance of the gut epithelium as a barrier to enteric infection. DEFA 1–4 are called Human Neutrophil Peptides 1–4 as they are most often expressed by neutrophils, commonly making up as much as 50% of the total protein content in these cells (Date et al, 1994; Faurschou and Borregaard, 2003). DEFA 5 and 6, known as Human Defensin 5 and Human Defensin 6, are produced only by Paneth cells (see Glossary) of the small intestine (Lisitsyn et al, 2012) It is still unclear whether the expression of HD5 and HD6 is consistent along the length of the small intestine. It is possible that there may be differences in human enteric defensin composition along the length of the small intestine which may impact the local microbiota (Nakamura et al, 2016)
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