Gut motor function: immunological control in enteric infection and inflammation

Abstract

Alteration in gastrointestinal (GI) motility occurs in a variety of clinical settings which include acute enteritis, inflammatory bowel disease, intestinal pseudo-obstruction and irritable bowel syndrome (IBS). Most disorders affecting the GI tract arise as a result of noxious stimulation from the lumen via either microbes or chemicals. However, it is not clear how injurious processes initiated in the mucosa alter function in the deeper motor apparatus of the gut wall. Activation of immune cells may lead to changes in motor-sensory function in the gut resulting in the development of an efficient defence force which assists in the eviction of the noxious agent from the intestinal lumen. This review addresses the interface between immune and motor system in the context of host resistance based on the studies in murine model of enteric nematode parasite infection. These studies clearly demonstrate that the infection-induced T helper 2 type immune response is critical in producing the alterations of infection-induced intestinal muscle function in this infection and that this immune-mediated alteration in muscle function is associated with host defence mechanisms. In addition, by manipulating the host immune response, it is possible to modulate the accompanying muscle function, and this may have clinical relevance. These observations not only provide valuable information on the immunological control of gut motor function and its role in host defence in enteric infection, but also provide a basis for understanding pathophysiology of gastrointestinal motility disorders such as in IBS.

Fig. 1

Response of intestinal muscle from control and T. spiralis infected rats. (a) Dose–response relationships for carbachol-induced tension generation by intestinal muscle from control non-infected (○) and T. spiralis infected (•) rats. Rats were infected orally with T. spiralis and killed at day 6 postinfection [12]. (b) Light micrographs of cross sections of muscularis externa of rat jejunum before and after T. spiralis infection, showing increased size of longitudinal and circular smooth muscle layers in the inflamed jejunum [14]

Fig. 2

(a) Intestinal muscle contraction and cytokine response in T. spiralis infected Stat6 deficient (Stat6−/−) and wild type (Stat6+/+) mice [29]. (b) Cytokines gene expression in muscularis externa of uninfected control (lanes 1–3) and T. spiralis-infected (lanes 4–6) mice. C57BL/6 mice were infected with T. spiralis orally and killed on day 6 p.i. to investigate expression of the IL-4, IL-13, and IFN-γ genes [29]. (c) IL-4 receptor (IL-4R) mRNA expression in dispersed longitudinal smooth muscle cells from control and T. spiralis-infected mice. sIL-4R, soluble IL-4R; mIL-4R, membrane IL-4R [30].

Fig. 3

Conceptual model of the interface between the immune and motor systems in the gastrointestinal (GI) tract, and the putative role of this interface in host defence. Infection produces mucosal injury and inflammation and induces an immune response. The Th2 type immune response induces changes in the intestinal muscle contractility in response to physiological stimuli such as the release of acetylcholine from the enteric nerves. The resulting increase in propulsive forces contributes to the eviction of the infective agent from the GI tract. Not shown are other components of motility apparatus including other enteric nerves, interstitial cells of Cajal and enteroendocrine cells.