Mucus: a slippery slope for worms
Hasnain, S.Z., Wang, H., Ghia, J.E., Haq, N., Deng, Y., Velcich, A., Grencis, R.K., Thornton, D.J., and Khan, W.I. 2010. Mucin Gene Deficiency in Mice Impairs Host Resistance to an Enteric Parasitic Infection. Gastroenterology. 138: 1763-71. pubmed
Infections by intestinal whipworms are a major public health problem, mainly in the developing world, infecting about a billion people worldwide, as well as their pets and cattle. Some people are susceptible to worm infection and develop a long-term chronic infection, however, others are resistant to infection and are able to expel the worms before they fully develop. Mucus, the slimy material that blankets the surface of the intestine, forms a protective barrier that is an important part of our innate immune system. About 25 years ago, scientists discovered that worms expelled in faeces are often covered in mucus produced by cells lining the intestine. This observation led to the hypothesis that mucus may have the ability to trap the worms before they can become established in the intestine.
The role of mucus in protecting against whipworm infection has been studied in Manchester using a mouse model that closely mimics the human infection. Mucus is not simply slime, but a complex mixture of salts, water and large sugar-coated proteins called mucins. These mucin molecules give mucus its gel-like properties, and they are produced by specialised cells known as goblet cells. In our experiments we saw 3 major differences between the resistant and susceptible groups of mice after infection with worms: 1) resistant mice had no worms, but had more mucus producing goblet cells, 2) the intestines of the resistant mice had more mucus, 3) the mucus of infected resistant mice contained a mucin that is not usually produced in the intestine. Furthermore, these changes were seen just before the worms were expelled, which suggests that they are involved in getting rid of the worms from the intestine. The increase in the amount of mucus and/or the introduction of a new mucin into the mucus barrier drastically alters the properties of the mucus and can have an effect on the health of the worms. More studies are now underway to try and understand what triggers these changes in the mucus barrier during worm expulsion and whether these can be induced in mice that are normally susceptible to worms and to make them resistant to infection. Overall, we have shown for the first time that the changes in the intestinal mucus barrier are an important part of a well co-ordinated response to get rid the worms.