Perspectives Series: Host/Pathogen Interactions

Mucosal surfaces of the intestinal, respiratory, and genitourinary tracts are the most important route of entry of microbial pathogens into the host, and are important sites of microbially induced disease. Mucosal infections with microbial pathogens can result in a spectrum of disease manifestations that range from mild and self-limited to fulminant and lethal, or can be chronic and debilitating. The latter may occur in response to repetitive infections and eventually lead to organ dysfunction. The variability in outcome is determined by differences in the virulence of the infecting pathogens, and the effectiveness of the host response. Epithelial cells that line mucosal surfaces are an important mechanical barrier that separates the host’s internal milieu from the external environment, as most microbes found in the environment, including commensals in the large bowel, do not enter epithelial cells. In addition to barrier functions, epithelial cells at different mucosal sites (e.g., urinary, bladder, and small intestine) and at different locations within a given organ system (e.g., stomach and colon) have specialized host adaptive functions. In the gastrointestinal tract, for example, epithelial cells have an important role in ion transport and fluid absorption and secretion. For pathogens that invade the host, epithelial cells are the first site of contact with the host, which is relevant for this article. Studies over the past several years have clearly indicated the integral role that epithelial cells at mucosal surfaces play in generating and transmitting signals between both invasive and noninvasive microbial pathogens, and adjacent and underlying cells in the mucosa. This led to the concept of epithelial cells as an integral component of a communications network that involves interactions between epithelial cells, luminal microbes, and host immune and inflammatory cells. This article focuses on the role epithelial cells play in this communication network as sensors of the intestinal microflora and providers of signals to the host that can affect the growth, development, and function of cells in the adjacent and underlying mucosa, and activate mucosal inflammatory and immune responses. This subject is divided into a section covering the repertoire of intestinal epithelial responses relevant for initiating and regulating the mucosal inflammatory and immune response (the host perspective), and a section on the pathophysiologic conditions under which these epithelial responses occur (the pathogen perspective). The reader is alerted to other important studies that have examined the expression of proinflammatory genes in epithelial cells of the respiratory and urinary tract (1, 2).