Paneth cells provide host defense against microbes in the small intestine. They are functionally similar to neutrophils. When exposed to bacteria or bacterial antigens, Paneth cells secrete a number of antimicrobial molecules into the lumen of the crypt, thereby contributing to maintenance of the gastrointestinal barrier.
Small intestinal crypts house stem cells that serve to constantly replenish epithelial cells that die and are lost from the villi. Protection of these stem cells is essential for long-term maintainance of the intestinal epithelium, and the location of Paneth cells adjacent to stem cells suggests that they play a critical role in defending epithelial cell renewal.
The principal defense molecules secreted by Paneth cells are alpha-defensins, also known as cryptdins. These peptides have hydrophobic and positively-charged domains that can interact with phospholipids in cell membranes. This structure allows defensins to insert into membranes, where they interact with one another to form pores that disrupt membrane function, leading to cell killing. Due to the higher concentration of negatively-charged phospholipids in bacterial membranes than vertebrate membranes, defensins preferentially bind to and disrupt bacterial cells, sparing the cells they are functioning to protect.
Paneth cells are stimulated to secrete defensins when exposed to bacteria (both Gram positive and negative types) or such bacterial products as lipopolysaccharide, muramyl dipeptide and lipid A. These cells also secrete lysozyme and phospholipase A2, both of which have clear antimicrobial activity. This battery of secretory molecules gives Paneth cells a potent arsenal against a broad spectrum of agents, including bacteria, fungi and even some enveloped viruses.
In addition to their role in defense with in the intestinal crypts, Paneth cells appear capable of responding to intestinal insults by changing into proliferative cells with stem cell-like character that assist in tissue repair.
References and Reviews
- Ayabe T, Satchell DP, Wilson CL, etc: Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Nature Immunol 2000; 1:113-118.
- Ganz T: Paneth cells--guardians of the gut cell. Nature Immunol 2000; 1:99-100.
- Roth S, Franken P, Sacchetti A, etc. Paneth cells in intestinal homeostasis and tissue injury. PLoS One 2012, http://dx.doi.org/10.1371/journal.pone.0038965.
- van der Flier LG and Clevers H. Stem cells, self rewnewal, and differentiation in the intestinal epithelium. Ann Rev Physiol 2009; 71:241-260.
- Wilson CL, Ouellette AJ, Satchell DP, etc: Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 1999; 286:113-117.
Back to: Small Intestine: Introduction and Index >
Send comments to Richard.Bowen@colostate.edu