Graphical Abstract Highlights d Maternal immunization confers protection to offspring against C. rodentium infection d Maternal IgG in breast milk, but not IgA or IgM, is required for neonatal protection d Maternal IgG coats the pathogen and increases its engulfment by neutrophils d LEE-specific antibodies are required to confer protection in the offspring Authors In Brief Caballero-Flores et al. demonstrate that maternal immunization with heatinactivated C. rodentium or surface pathogen antigens protects neonatal mice against pathogen oral challenge. Protection was mediated by the delivery of pathogen-specific IgG through breast milk, which coated the pathogen, increased its phagocytosis, and decreased epithelial attachment in the gut.

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Host immunity limits iron availability to pathogenic bacteria, but whether immunity limits pathogenic bacteria from accessing host heme, the major source of iron in the body, remains unclear. Using Citrobacter rodentium, a mouse enteric pathogen and Escherichia coli, a major cause of sepsis in humans as models, we find that interleukin-22, a cytokine best known for its ability to promote epithelial barrier function, also suppresses the systemic growth of bacteria by limiting iron availability to the pathogen. Using an unbiased proteomic approach to understand the mechanistic basis of IL-22 dependent iron retention in the host, we have identified that IL-22 induces the production of the plasma hemoglobin scavenger haptoglobin and heme scavenger hemopexin. Moreover, the anti-microbial effect of IL-22 depends on the induction of hemopexin expression, while haptogloblin is dispensable. Impaired pathogen clearance in infected Il22−/− mice was restored by hemopexin administration and hemopexin-deficient mice had increased pathogen loads after infection. These studies reveal a previously unrecognized host defense mechanism regulated by IL-22 that relies on the induction of hemopexin to limit heme availability to bacteria leading to suppression of bacterial growth during systemic infections.

Highlights d Tn-seq screen revealed genes required for pathogen expansion in the mouse gut d The microbiota depletes the gut of amino acids, limiting their availability d C. rodentium induces amino acid biosynthesis for its expansion in the gut d Administration of a high protein diet promotes pathogen colonization in mice