Journal
NATURE IMMUNOLOGY
Volume 19, Issue 10, Pages 1100-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41590-018-0211-2
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Funding
- Snyder Mouse Phenomics Resources Laboratory - Snyder Institute for Chronic Diseases at the University of Calgary
- Alberta Innovates Health Solutions
- Canadian Institutes of Health Research
- Canada Research Chairs Program
- Live Cell Imaging Facility - Snyder Institute for Chronic Diseases at the University of Calgary
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Females have an overall advantage over males in resisting Gram-negative bacteremias, thus hinting at sexual dimorphism of immunity during infections. Here, through intravital microscopy, we observed a sex-biased difference in the capture of blood-borne bacteria by liver macrophages, a process that is critical for the clearance of systemic infections. Complement opsonization was indispensable for the capture of enteropathogenic Escherichia coli (EPEC) in male mice; however, a faster complement component 3-independent process involving abundant preexisting antibodies to EPEC was detected in female mice. These antibodies were elicited predominantly in female mice at puberty in response to estrogen regardless of microbiota-colonization conditions. Estrogen-driven antibodies were maternally transferrable to offspring and conferred protection during infancy. These antibodies were conserved in humans and recognized specialized oligosaccharides integrated into the bacterial lipopoly-saccharide and capsule. Thus, an estrogen-driven, innate antibody-mediated immunological strategy conferred protection to females and their offspring.
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