Your most powerful defense against the perils of undercooked chicken may already be hidden in your gut. A recent study has found that a naturally produced intestinal peptide can have a substantial impact on the body's ability to fight off Salmonella infection, as demonstrated in a transgenic mouse model.

Researchers at the Medical College of Wisconsin (Milwaukee) and Lerner Research Institute (Cleveland, OH) have developed a transgenic mouse line that overexpresses HD-5, a human peptide normally produced in specialized niches within the small intestinal wall by cells known as Paneth cells. These cells store HD-5 as an inactive propeptide, which undergoes cleavage before secretion into the intestinal lumen. Thus activated, HD-5 is thought to play an important role in the body's innate defenses against bacterial infection.

Confirming this theory were studies showing that the HD-5 transgenics showed considerably elevated resistance to the ravages of Salmonella typhimurium infection (Nature, 3 April). Transgenic mice treated with 108 colony-forming units (c.f.u.) of virulent bacteria retained considerably lower densities of intestinal S. typhimurium than wild-type animals. After challenge with greater numbers of bacteria (1.5 × 109 c.f.u.), wild-type mice showed significant external signs of illness, and all died within 24 h of oral inoculation. By comparison, the transgenic mice showed milder symptoms, and all mice recovered within 12 h after the initial inoculation. Biochemical studies showed that the transgenic mice were properly expressing and processing HD-5; furthermore, the peptide's ability to combat S. typhimurium infection was eliminated when the bacteria were introduced intraperitoneally, confirming that the small intestine is HD-5's primary site of action.

These results complement a growing body of data supporting an important role for mammalian antimicrobial peptides in staving off bacterial infection, and suggest a potentially valuable therapeutic target for the augmentation of innate host immunity.