A challenge faced by intestinal cells is that they must tolerate commensal bacteria, with which they have a mutualistic relationship (Backhed et al., 2005; Dale and Moran, 2006; Sansonetti and Medzhitov, 2009) , while also mounting a vigorous response to pathogens (for a review, see Ryu et al., 2010) . One important pathway involved in this distinction controls the production of reactive oxygen species (ROS) by the dual-oxidase (Duox) transmembrane protein (Ha et al., 2009; Ha et al., 2005a; Ha et al., 2005b) , which also plays a key role in the human gut (for a review, see Ryu et al., 2010) . Genetic analysis in Drosophila has revealed bi-stable control of Duox activity in the gut. In the presence of commensal bacteria and absence of pathogenic species, low-level activation of the immune deficiency (IMD) pathway of the innate immune system (see later) induces negative feedback of the Duox pathway (at both the level of expression and activity), resulting in low basal levels of ROS production. By contrast, when invading pathogens are detected by host immune signaling, expression and activity of Duox components is greatly increased, leading to destruction of the pathogenic bacteria (Ha et al., 2009) .