In one screen using adult flies, host defense factors that are required to protect against intestinal infection with the opportunistic broad-host-spectrum pathogen Serratia marcescens were first identified by using a large collection of fly lines in which 13,000 individual RNAi molecules were used to knock down target gene expression throughout the organism (Cronin et al., 2009) . RNAi molecules that caused increased lethality following infection were then tested further for their role in defending Host-pathogen interactions in Drosophila PERSPECTIVE against S. marcescens infection of the gut by expressing the relevant UAS-RNAi constructs with gut-specific and hemocytespecific drivers. These studies first confirmed the dependence on the IMD (but not Toll) innate immune pathway for responding to infection by S. marcescens (as would be expected for a Gramnegative bacterium), and also revealed an important role for the JAK-STAT pathway in responding to infection in the gut (Fig. 2C ). Further analysis of JAK-STAT signaling showed that this pathway regulates stem cell proliferation and thereby intestinal epithelial homeostasis during infection. These results obtained in intact flies provide an important complement to screens performed in C. elegans, which also identified several signaling systems important for innate immunity (Irazoqui et al., 2010) . Studies of damage and repair by gut pathogens can be conducted in Drosophila because flies, but not worms, have intestinal stem cells that replenish epithelial cells after they undergo programmed cell death during infection (see above).