AMPlifying type 2 immunity Antimicrobial proteins (AMPs) are a frontline defense against pathogenic microorganisms at mucosal surfaces. These cationic molecules inactivate their targets primarily by disrupting cell walls and membranes. Hu et al . found that small proline-rich protein 2A (SPRR2A) is a bactericidal protein produced in the gut that targets Gram-positive bacteria and is phylogenetically distinct from all other known AMPs (see the Perspective by Harris and Wickramasinghe). SPRR2A production is selectively enhanced by type 2 cytokines such as interleukin-4 and -13 that are elicited by helminth infection. Mice lacking SPRR2A are unable to prevent intestinal bacteria from invading the intestinal barrier after helminths damage the intestinal epithelium. SPRR2A is thus a critical component of type 2 immunity that protects against the bacterial invasion and dissemination that follow helminth infection. —STS