Eosinophils drive intestinal remodelling and innate defence in reproduction

Mammalian reproduction requires substantial immune adaptations to safeguard reproductive success and to ultimately shape the evolutionary trajectories of a species. Systemic and placental immunity shift towards tolerance during pregnancy1,2; however, how maternal immunity adapts in barrier tissues—which are sites of frequent infection and inflammation—from pregnancy until the postpartum lactation period remains poorly understood. Here we report a previously unrecognized role for eosinophils, a type of granulocyte typically associated with allergies and helminth infections3,4, in remodelling the intestinal barrier during reproduction. Beginning in pregnancy and peaking during lactation, eosinophils accumulate in the small intestine in the absence of infection or inflammation. Using genetic and pharmacological perturbations, organoid cultures and single-cell and spatial transcriptomics, we show that eosinophils promote goblet cell differentiation in a stem-cell-intrinsic manner that leads to increased mucus production. This remodelling culminates during lactation and limits pathogen entry and dissemination to confer broad innate protection against enteric bacterial infections. Moreover, in mice, intestinal remodelling and innate defence persist weeks after lactation cessation. Our findings demonstrate that despite a general trend towards systemic immune modulation during reproduction, the maternal intestine undergoes remodelling to strengthen innate defence, a mechanism that may have evolved to protect mothers and offspring in pathogen-rich environments. More broadly, we establish a framework for studying tissue-specific immune adaptation across the reproductive cycle and highlight that tissues can retain changes following physiological reproduction, with lasting implications for host defence and women’s health. From pregnancy until lactation, eosinophils accumulate in the small intestine where they regulate goblet cell fate and enhance innate defences against enteric pathogens.