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Ending the War Metaphor: The Changing Agenda for Unraveling the Host-Microbe Relationship - Workshop Summary
host-microbe interactions through the use of molecular techniques that monitor microbial and host cell gene expression. In his contribution to this chapter, David Relman describes studies conducted in his laboratory that employ DNA microarrays to monitor host transcript abundance in blood cells following exposure to known bacterial and viral pathogens. Their findings illustrate variation in the indigenous microbial flora of healthy humans and the range of host transcriptional response to infection; Relman and colleagues also identify recurring patterns and possible sources of variability in that response. Relman also describes the use of rDNA polymerase chain reaction (PCR) to explore the possible pathogenic activity of archaea, focusing on their potential role in peridontitis.
One factor that has not been found to produce significant differences in host gene expression is the distinction between pathogen- versus commensal-associated stimuli. Detailed comparisons of host transcriptional responses to various pathogens over time are, however, revealing subtle transcriptional signatures upon the host response. Such variability—which is thought to result from pathogen-specific mechanisms that co-opt, subvert, or modify the stereotypical host response to microbial stimuli—offers the possibility of a new approach to disease prevention, diagnosis, and treatment.
THE INTESTINAL EPITHELIUM: AN INTERACTIVE BARRIER BETWEEN HOST AND MICROBE
Those of us who study mucosal immunity and mucosal protection are in the habit of using the war metaphor when we talk about the epithelial monolayer that lines the human gut. We have described it as a barrier and the mucus it secretes as our “front line” of defense. However, this impression is being revised as we discover that the intestinal epithelium also acts as a sensor of the contents of the lumen, and as an “intelligent” mediator of immune signaling between ourselves and the microbes we encounter.
By “intelligent,” I mean that the intestinal epithelium appears capable of filtering a tremendous amount of information regarding the antigens borne by the huge and diverse population of microorganisms in the lumen. Specialized epithelial cells survey the contents of the gut and report it to a highly developed mucosal immune recognition system that resides in adjacent lymphoid cells—and, remarkably, this occurs without provoking all-out war in the form of chronic intestinal inflammation. The following essay recounts several recent discoveries that show how these specialized intestinal epithelial cells accomplish this critical balancing act.