Defensins and innate host defence of the gastrointestinal tract

When viewed from the perspective of host defence, the mammalian digestive tract presents many challenges. At the outset food contains various micro-organisms that could thrive in the rich growth medium of digested nutrients. Because a large surface area is required for the absorption of nutrients, there are abundant potential sites for microbial attachment and invasion in the long digestive tube with its many folds, villi and microvilli. The requirements of efficient nutrient absorption also place limits on the barrier components of host defence. Indeed, unlike the skin, vaginal epithelium or oral mucosa, intestinal mucosa is comprised of only a single layer of epithelial cells. This delicate barrier is further threatened by the effects of acid, bile salts, and hydrolytic enzymes required for digestion. Although some of these molecules are toxic to microbes, and hence may help to control microbial proliferation and survival, these agents may also subtly damage the mucosa and compromise its barrier functions. The potential for cumulative damage may explain why this epithelium is rapidly and continually replaced throughout the lifetime of mammals. As a result of the need for epithelial renewal, stem cell proliferation and differentiation are critical for normal function of the gastrointestinal tract. Damage to, or parasitisation of stem cells would have severe consequences for the maintenance of the normal digestive epithelium. A continuous microbial threat is also posed by a wide array of colonising microbes throughout the gut, with especially large numbers in the mouth and colon. Infectious complications that often follow treatment with antibiotics suggest that colonising symbionts contribute to host defence against pathogens. Yet, in the absence of effective defence mechanisms, even symbiotic microbes can multiply rapidly and overwhelm the mammalian host. Despite the presence of microbes, normal digestive tract surfaces generally show little evidence of inflammation, the coordinated pattern of vasodilatation, …