A vast and diverse array of microbes colonizes the mammalian gastrointestinal tract. These microorganisms are integral in shaping the development and function of the immune system. Metagenomic sequencing analysis has revealed alterations in intestinal microbiota in patients suffering from chronic inflammatory diseases, including inflammatory bowel disease and asthma. This review will discuss the mechanisms through which the innate immune system recognizes and responds to the intestinal microbiota as well as the effect of specific microbiota-derived signals on immune cell homeostasis. Recent studies in murine model systems have demonstrated that manipulation of the intestinal microbiota can alter mammalian immune cell homeostasis. Specific microbial signals have been identified that can impact immune cell function both within the intestinal tract and in peripheral tissues. These microbiota-derived signals can either have an immunoregulatory effect, creating an immune state that is refractory to inflammation, or conversely, act as an adjuvant, aiding in the propagation of an immune response. Associations between alterations in the microbiota and human disease implicate intestinal microbial signals in shaping immune responses. These signals are recognized by innate immune cells and influence the ability of these cells to modulate both the local and systemic immune response.
