Hooking into antigen transfer Segmented filamentous bacteria (SFB) are anaerobic, spore-forming, clostridia-like organisms that are important immune modulators in the mammalian gut. For some reason, SFB do not provoke inflammatory responses. Ladinsky et al. probed the mechanistic basis of this soothing effect in mice. SFB attach tightly to intestinal epithelial cells via a hook-like structure. Bacterial material is extruded from the hook and enters the host cell by endocytosis. An extruded SFB protein called P3340 is shuttled by the host protein cell division control protein 42 homolog (CDC42) through the endosomelysosome vesicular pathway to the basolateral side of the intestinal epithelial cell. Here, it prompts an immunomodulatory SFB-specific CD4 T helper 17 cell response, possibly via intestinal macrophages. Science , this issue p. eaat4042