Nature：正常菌群诱导的母源IgG，通过母乳保护后代抵御感染
- ①来自母鼠的母源天然抗体，可保护无法产生IgA和IgG抗体的新生鼠，抵御肠产毒素大肠杆菌（ETEC）的肠内定植和感染，母乳中的IgG起关键作用；
- ②新生鼠肠上皮表达Fc受体（FcRn），不同于成鼠，新生鼠可将母乳中的IgG经FcRn从肠腔转运至血液；
- ③母源抗体的产生依赖于其正常菌群，菌群中的特定成员（如肠杆菌科的Pantoea菌属）可诱导母鼠产生识别ETEC等其它肠杆菌科细菌的交叉反应性抗体，足以保护仔鼠抵抗ETEC。
主编推荐语
新生儿由于还不具有成熟的免疫系统和正常菌群，对致病微生物的抵抗力较弱，这一时期来自母亲的抗体对于帮助新生儿抵抗感染至关重要。比如，母亲注射疫苗产生的特定IgG抗体，可通过胎盘与母乳传递给后代。Nature最新发表来自美国哈佛大学Dennis Kasper与John Mekalanos合作团队的研究（Wen Zheng博士和中山大学赵文婧教授为共同第一作者），揭示了母源天然抗体（即不是通过接触病原体所获得的抗体）在保护新生儿中的作用和机制。这项研究通过巧妙的小鼠试验发现，正常菌群可诱导母鼠产生抗特定致病菌（比如抗产肠毒素大肠杆菌）的交叉免疫性IgG抗体，这些抗体通过母乳传递给仔鼠，并能在仔鼠中从肠腔转移到血液，从而帮助仔鼠抵抗致病菌引发的肠道和系统性感染。这些发现揭示了母乳喂养对新生儿的抗感染保护作用的关键分子机制，同时也将两代宿主肠道菌群通过母源抗体关联起来，开辟了新的研究领域。
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Microbiota-targeted maternal antibodies protect neonates from enteric infection
靶向菌群的母源抗体保护新生儿抵御肠道感染
10.1038/s41586-019-1898-4
2020-01-08, Article
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Although maternal antibodies protect newborn babies from infection12, little is known about how protective antibodies are induced without prior pathogen exposure. Here we show that neonatal mice that lack the capacity to produce IgG are protected from infection with the enteric pathogen enterotoxigenic Escherichia coli by maternal natural IgG antibodies against enterotoxigenic E. coli when antibodies are delivered either across the placenta or through breast milk. By challenging pups that were fostered by either maternal antibody-sufficient or antibody-deficient dams, we found that breast-milk-derived IgG was critical for protection against mucosal disease induced by enterotoxigenic E. coli. IgG also provides protection against systemic infection by E. coli. Pups used the neonatal Fc receptor (FcRn) to transfer IgG from milk into serum. The maternal commensal microbiota can induce antibodies that recognize antigens expressed by enterotoxigenic E. coli and other Enterobacteriaceae species. Induction of maternal antibodies against a commensal Pantoea species confers protection against enterotoxigenic E. coli in pups. This role of the microbiota in eliciting protective antibodies to a specific neonatal pathogen represents an important host defence mechanism against infection in neonates.
First Authors:
Wen Zheng,Wenjing Zhao
Correspondence Authors:
Dennis L Kasper
All Authors:
Wen Zheng,Wenjing Zhao,Meng Wu,Xinyang Song,Florence Caro,Ximei Sun,Francesca Gazzaniga,Giuseppe Stefanetti,Sungwhan Oh,John J Mekalanos,Dennis L Kasper
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