Bacterial effectors that are secreted into the host cell cytosol can induce a protective immune response, according to a new study. The authors found that cytotoxic necrotizing factor 1 (Cnf1), a uropathogenic Escherichia coli (UPEC) toxin that activates RHO GTPases, induces the production of antimicrobial peptides when expressed in Drosophila melanogaster cells. Furthermore, flies challenged with wild-type UPEC mounted a vigorous immune response, whereas bacteria lacking Cnf1 did not induce such a response, and the Cnf1-induced immune response protected flies from the lethal effects of infection by Pseudomonas aeruginosa str. PA14. Further analysis revealed that the immune activation is a response to the changed activation of RAC2 and requires the immunedeficiency (IMD) pathway. A similar response to the toxin was detected in mammalian cells, in which it depended on the kinases RIP1 and RIP2 (also known as RIPK1 and RIPK2, respectively). Hence, the presence of a bacterial toxin is detected by its effects on the host and induces a protective immune response. The authors suggest that such a response is similar to the response of plants to pathogen effectors.