Calvin Phoebe & Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Department of Physiology and Pharmacology Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Nat Immunol. 2018 Oct;19(10):1100-1111. doi: 10.1038/s41590-018-0211-2. Epub 2018 Sep 24.
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 lipopolysaccharide and capsule. Thus, an estrogen-driven, innate antibody-mediated immunological strategy conferred protection to females and their offspring.
女性在抵抗革兰氏阴性菌血症方面具有整体优势，这表明在感染过程中免疫存在性别二态性。在这里，通过活体显微镜观察到，在肝脏巨噬细胞捕获血源细菌的过程中存在性别差异，这一过程对于清除全身感染至关重要。补体调理对于捕获肠致病性大肠杆菌（EPEC）在雄性小鼠中是必不可少的；然而，在雌性小鼠中检测到了一种更快的补体成分 3 非依赖性过程，涉及大量针对 EPEC 的预先存在的抗体。这些抗体主要在雌性小鼠进入青春期时产生，这是对雌激素的反应，而与微生物定植条件无关。雌激素驱动的抗体可经母体传递给后代，并在婴儿期提供保护。这些抗体在人类中是保守的，可识别整合到细菌脂多糖和荚膜中的特异性寡糖。因此，一种由雌激素驱动的、先天抗体介导的免疫策略为女性及其后代提供了保护。
