Liver macrophages and sinusoidal endothelial cells execute vaccine-elicited capture of invasive bacteria

调理素 抗体 免疫系统 免疫 抗体调理 生物 免疫学 免疫球蛋白G 微生物学 补体受体 补体系统 受体 Fc受体 生物化学
作者
Juanjuan Wang,Haoran An,Ming Wei Ding,Yanhong Liu,Shaomeng Wang,Qian Jin,Qi Wu,Haodi Dong,Qile Guo,Xianbin Tian,Jiankai Liu,Jingfei Zhang,Tao Zhu,Junqiang Li,Zhujun Shao,David E. Briles,Jan‐Willem Veening,Haifa Zheng,Linqi Zhang,Jing‐Ren Zhang
出处
期刊:Science Translational Medicine [American Association for the Advancement of Science (AAAS)]
卷期号:15 (727) 被引量:5
标识
DOI:10.1126/scitranslmed.ade0054
摘要

Vaccination has substantially reduced the morbidity and mortality of bacterial diseases, but mechanisms of vaccine-elicited pathogen clearance remain largely undefined. We report that vaccine-elicited immunity against invasive bacteria mainly operates in the liver. In contrast to the current paradigm that migrating phagocytes execute vaccine-elicited immunity against blood-borne pathogens, we found that invasive bacteria are captured and killed in the liver of vaccinated host via various immune mechanisms that depend on the protective potency of the vaccine. Vaccines with relatively lower degrees of protection only activated liver-resident macrophage Kupffer cells (KCs) by inducing pathogen-binding immunoglobulin M (IgM) or low amounts of IgG. IgG-coated pathogens were directly captured by KCs via multiple IgG receptors FcγRs, whereas IgM-opsonized bacteria were indirectly bound to KCs via complement receptors of immunoglobulin superfamily (CRIg) and complement receptor 3 (CR3) after complement C3 activation at the bacterial surface. Conversely, the more potent vaccines engaged both KCs and liver sinusoidal endothelial cells by inducing higher titers of functional IgG antibodies. Endothelial cells (ECs) captured densely IgG-opsonized pathogens by the low-affinity IgG receptor FcγRIIB in a “zipper-like” manner and achieved bacterial killing predominantly in the extracellular milieu via an undefined mechanism. KC- and endothelial cell–based capture of antibody-opsonized bacteria also occurred in FcγR-humanized mice. These vaccine protection mechanisms in the liver not only provide a comprehensive explanation for vaccine-/antibody-boosted immunity against invasive bacteria but also may serve as in vivo functional readouts of vaccine efficacy.
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