Eosinophils drive intestinal remodelling and innate defence in reproduction

While systemic immune tolerance is a well-known feature of pregnancy, the state of maternal immunity in barrier tissues—such as the gut—during the postpartum lactation period remains poorly understood. This study investigates how the maternal intestine adapts to balance the physiological demands of reproduction with the need to defend against environmental pathogens.

Using a hormone-induced mouse model of pregnancy and lactation, the researchers performed a comprehensive analysis of the intestinal immune landscape. They employed multiparameter flow cytometry, single-cell RNA sequencing, and spatial transcriptomics (10x Genomics Xenium) to identify changes in immune cell populations and epithelial composition. To determine the functional role of these changes, they used genetic (eosinophil-deficient mice) and pharmacological (anti-CCR3) perturbations, followed by oral challenge with foodborne pathogens like Yersinia pseudotuberculosis and Salmonella Typhimurium.

The researchers discovered that eosinophils accumulate significantly in the proximal small intestine during pregnancy and peak during lactation. These eosinophils do not cause inflammation; instead, they act as homeostatic regulators that reprogram intestinal stem cells to differentiate into goblet cells. This leads to increased mucus production, which fortifies the intestinal barrier. Consequently, lactating mice exhibit superior resistance to enteric pathogens, showing reduced bacterial colonization and systemic dissemination. Remarkably, this remodelling is not transient; the increased eosinophil and goblet cell populations, along with enhanced innate defence, persist for weeks after the cessation of lactation.

This study challenges the traditional view that reproduction solely increases susceptibility to infection. By identifying a mechanism where the maternal gut is actively 'primed' for enhanced innate defence, the authors provide a new framework for understanding how physiological states can leave lasting imprints on tissue immunity. These findings have significant implications for women's health, suggesting that reproduction may permanently alter host defence strategies in ways that could influence long-term resilience to gastrointestinal infections.