http://journals.cambridge.org Downloaded: 15 Jul 2009 IP address: 136.159.235.223 REVIEW ARTICLE Physiological changes in the gastrointestinal tract and host protective immunity : learning from the mouse-Trichinella spiralis model W. I. KHAN* Intestinal Disease Research Program, Department of Medicine, McMaster University, Hamilton, Ontario, Canada (Received 28 January 2008; revised 12 February 2008; accepted 13 February 2008) SUMMARY Infection and inflammation in the gastrointestinal (GI) tract induces a number of changes in the GI physiology of the host. Experimental infections with parasites represent valuable models to study the structural and physiological changes in the GI tract. This review addresses research on the interface between the immune system and GI physiology, dealing specifically with 2 major components of intestinal physiology, namely mucin production and muscle function in relation to host defence, primarily based on studies using the mouse-Trichinella spiralis system. These studies demonstrate that the infection-induced T helper 2 type immune response is critical in generating the alterations of infection-induced mucin production and muscle function, and that this immune-mediated alteration in gut physiology is associated with host defence mechanisms. In addition, by manipulating the host immune response, it is possible to modulate the accompanying physiological changes, which may have clinical relevance. In addition to enhancing our understanding of immunological control of GI physiological changes in the context of host defence against enteric infections, the data acquired using the mouse-T. spiralis model provide a basis for understanding the pathophysiology of a wide range of GI disorders associated with altered gut physiology. Key words: Trichinella spiralis, immunophysiology, infection, immunity, mucin, muscle. INTRODUCTION Changes in gastrointestinal (GI) physiology are a prominent feature of many GI disorders, which in- clude infections by a variety of infectious agents (bacteria, viruses and parasites), chronic inflam- matory bowel diseases (IBDs) and functional dis- orders such as irritable bowel syndrome (IBS). These changes include goblet cell hyperplasia and increased mucin secretion, increased fluid secretion and enhanced intestinal propulsive activity. How- ever, little is known about the mechanisms of these changes in gut physiology or the precise role of these changes in host defence. Mucosal inflammation and immune activation in the gut by noxious agents may lead to changes in gut physiology, resulting in the development of an efficient defence which assists in the eviction of the noxious agent from the gut lumen. Some parasitic nematode infections are of con- siderable importance in exploring the pathophysi- ology of many GI disorders. In the past decade, our laboratory has used primary infection of rats or mice with the nematode Trichinella spiralis as a model for studying the interface between immune and gut physiological systems in the context of host defence and the underlying mechanisms involved. The choice of this model is based on the existence of an extensive body of literature regarding the in- flammatory and immune responses against this parasite (Table 1), and on the fact that many of the ingested parasites in this model are eventually ex- pelled from the gut, forcing attention on the role of the physiological system in promoting the expulsion of these parasites from the intestine. This article reviews information from the studies of the immunological control of 2 major components of the GI physiological system, namely smooth muscle and goblet cells during nematode infection in the context of host defence and highlight its impli- cation in understanding the pathophysiology of various GI disorders. ALTERATION OF GOBLET CELL FUNCTION AND MUCIN PRODUCTION IN NEMATODE INFECTION There is a continuous layer of mucus overlying the epithelium of the GI tract. This mucus layer has * Corresponding author : Department of Medicine, Room 3N5D, Health Science Center, McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada. E-mail : khanwal@mcmaster.ca 671 Parasitology (2008), 135, 671–682. f 2008 Cambridge University Press doi:10.1017/S0031182008004381 Printed in the United Kingdom