Gut feelings of safety: tolerance to the microbiota mediated by innate immune receptors

To enable microbial colonization of the gut mucosa, the intestinal immune system must not only react to danger signals but also recognize cues that indicate safety. Recognition of safety, paradoxically, is mediated by the same environmental sensors that are involved in signaling danger. Indeed, in addition to their well-established role in inducing inflammation in response to stress signals, pattern recognition receptors and a variety of metabolic sensors also promote gut-microbiota symbiosis by responding to microbial symbiosis factors, resolution-associated molecular patterns, markers of energy extraction and other signals indicating the absence of pathogenic infection and tissue damage. Here we focus on how the paradoxical roles of immune receptors and other environmental sensors define the microbiota signature of an individual.