Upregulation of Innate Defense Mechanisms by Enteric Infections

Abstract

This chapter examines the role of the intestinal epithelium in innate immune defense against enteric microbial pathogens. It focuses on in vitro and in vivo model systems that can be used to define epithelial cell innate immune defense mechanisms that are activated in response to microbial infection and a spectrum of intestinal epithelial innate defense mechanisms that can be activated by microbial pathogens that use different strategies to interact with the host. Interactions between enteric microbial pathogens and intestinal epithelial cells involve, by definition, two major players: the pathogen and the host epithelial cell. Invasive and noninvasive pathogens can activate epithelial cell signaling cascades that are essential for the development of innate defense. This involves a number of sophisticated evolutionary coevolved strategies on the part of the microbes and the host epithelial cells that are the targets of infection. Relevant to the activation of innate mucosal defense by intestinal epithelial cells, some of the members of one family of pattern-recognition receptors (PRR), the Toll-like receptors (TLR), are expressed by intestinal epithelial cells. Antimicrobial peptides and proteins are highly conserved in evolution and appear to play an important role in intestinal epithelial cell innate defense. Intestinal epithelial cells are an integral component of innate mucosal defense. In this role, they can produce antimicrobial peptides, chemokines, cytokines, nitric oxide (NO), and eicosanoids and express receptors for cytokines and pathogen-associated molecular patterns (PAMP), each of which can play a role in epithelial cell innate defense mechanisms.