Bacterial Colonization in the Development of Intestinal Host Defenses and in Clinical Disease
Bacterial Colonization in the Development of Intestinal Host Defenses and in Clinical Disease
US Gastroenterology Review 2006
Published: October 2008
Published: October 2008
The intestinal mucosa is the interface between the external and internal environments of a host that separates luminal antigens (bacteria, bacterial products, and food) of the gastrointestinal (GI) tract from the largest population of lymphocytes in the body. Soon after birth, the mucosal surfaces of the gut are quickly colonized by commensal bacteria. Colonization of the intestine with microbial flora plays an important role in stimulating the expansion of the lymphoid cell population and in induction of normal development of the immune system, including the gut-associated lymphoid tissues (GALTs).
Animals housed in a germ-free environment show impaired development of the immune system and weaker immune responses. Colonization of germ-free animals with intestinal commensal flora results in development of the immune system. It is clear that there is a complex relationship between the intestinal immune system and intestinal commensal flora. As mucosal surfaces are colonized by a large, complex, and dynamic collection of bacteria, it is extremely important for intestinal epithelial cells and the intestinal mucosal immune system to discriminate between pathogenic and non-pathogenic bacteria and generate an appropriate response, maintaining a state of homeostasis with normal microbial flora or initiating inflammatory responses against pathogens. It has been suggested that the cellular interactions between intestinal epithelial and immune cells are important in the initiation and regulation of the immune response to luminal bacterial antigens. Colonization of intestinal mucosal surfaces with a normal intestinal flora is purported to be necessary for the development of tolerance to dietary antigens,1 whereas certain intestinal bacteria (probiotics) have been hypothesized to have the potential to preferentially stimulate subsets of T helper cells (Th1,Th2) and thereby modify intestinal inflammatory and allergic responses.2
This article discusses the role of intestinal bacterial colonization in regulating the development and function of the intestinal mucosal immune system and in the pathogenesis of intestinal diseases.
GALTs are the largest collection of lymphoid tissues in the body, consisting of both organized lymphoid tissues, such as mesenteric lymph nodes (MLN) and Peyer’s patches (PP), and more diffusely scattered lymphocytes in the intestinal lamina propria (LP) and epithelium (see Figure 1), including large numbers of immunoglobulin (Ig)A+ plasmablasts.
Figure 1: Ontogeny of the Human Mucosal Immune System
This figure shows the major components of the mucosal immune system.The respective developmental time points for key components are highlighted. Note organized lymphoid tissue, such as Peyer’s patches (2) and more diffusely scattered lymphocytes in the intestinal lamina propria (3), and intraepithelial lymphocytes (4).This immune system is developmentally regulated.The development and function of the mucosal immune system can be affected by intestinal bacteria.
This figure shows the major components of the mucosal immune system.The respective developmental time points for key components are highlighted. Note organized lymphoid tissue, such as Peyer’s patches (2) and more diffusely scattered lymphocytes in the intestinal lamina propria (3), and intraepithelial lymphocytes (4).This immune system is developmentally regulated.The development and function of the mucosal immune system can be affected by intestinal bacteria.
