Microbial exposure during early human development primes fetal immune cells.
Microbial exposure during early human development primes fetal immune cells.
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人类早期发育过程中的微生物暴露引发胎儿免疫细胞。
DOI：
10.1016/j.cell.2021.04.039
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发表时间：
2021-06-24
期刊：
影响因子：
64.5
通讯作者：
Ginhoux F
中科院分区：
文献类型：
--
作者：
Mishra A;Lai GC;Yao LJ;Aung TT;Shental N;Rotter-Maskowitz A;Shepherdson E;Singh GSN;Pai R;Shanti A;Wong RMM;Lee A;Khyriem C;Dutertre CA;Chakarov S;Srinivasan KG;Shadan NB;Zhang XM;Khalilnezhad S;Cottier F;Tan ASM;Low G;Chen P;Fan Y;Hor PX;Lee AKM;Choolani M;Vermijlen D;Sharma A;Fuks G;Straussman R;Pavelka N;Malleret B;McGovern N;Albani S;Chan JKY;Ginhoux F
人类胎儿免疫系统在妊娠早期开始发育;然而，负责胎儿免疫启动的因素仍然难以捉摸。我们探讨了在子宫内暴露于微生物制剂的可能性及其对胎儿组织中记忆T细胞激活的贡献。我们使用16 S rRNA基因测序分析了胎儿器官中的微生物，并在妊娠第二个三个月的胎儿肠道，皮肤，胎盘和肺中检测到低但一致的微生物信号。我们在胎儿组织中鉴定了几种活细菌菌株，包括葡萄球菌和乳酸杆菌，它们在体外诱导胎儿肠系膜淋巴结中的记忆T细胞活化，支持微生物暴露在胎儿免疫启动中的作用。最后，利用扫描电镜和RNA原位杂交，我们可视化离散定位的细菌样结构和真细菌RNA在14周胎儿肠腔。这些发现表明，在妊娠第二个三个月期间，胎儿器官中选择性存在活微生物，并对出生前免疫能力的建立和启动具有更广泛的意义。妊娠中期的人类胎儿显示具有效应记忆表型的T细胞多样性。胎儿器官显示可以培养和繁殖的不同细菌属。EGA胎儿肠周胎儿细菌诱导胎儿mLN T细胞中的同系记忆T细胞活化妊娠第二个三个月的人胎儿组织和胎盘的分析鉴定了活细菌菌株，能够诱导胎儿肠系膜淋巴结中记忆T细胞的激活，从而提供对早期生命免疫的见解。
The human fetal immune system begins to develop early during gestation; however, factors responsible for fetal immune-priming remain elusive. We explored potential exposure to microbial agents in utero and their contribution toward activation of memory T cells in fetal tissues. We profiled microbes across fetal organs using 16S rRNA gene sequencing and detected low but consistent microbial signal in fetal gut, skin, placenta, and lungs in the 2nd trimester of gestation. We identified several live bacterial strains including Staphylococcus and Lactobacillus in fetal tissues, which induced in vitro activation of memory T cells in fetal mesenteric lymph node, supporting the role of microbial exposure in fetal immune-priming. Finally, using SEM and RNA-ISH, we visualized discrete localization of bacteria-like structures and eubacterial-RNA within 14th weeks fetal gut lumen. These findings indicate selective presence of live microbes in fetal organs during the 2nd trimester of gestation and have broader implications toward the establishment of immune competency and priming before birth. Human fetuses in 2nd trimester show T cell diversity with effector-memory phenotype Fetal organs show diverse bacterial genera that can be cultured and propagated Bacterial structures with mucin-like threads are visualized in 14-weeks EGA fetal gut Fetal bacteria induce syngeneic memory T cell activation in fetal mLN T cells Analysis of human fetal tissues and the placenta in the 2nd trimester of gestation identifies live bacterial strains that are able to induce the activation of memory T cells in the fetal mesenteric lymph node, thus providing insights into early life immunity.
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结合16S rRNA基因变量区域可以实现高分辨率微生物社区分析。
影响因子：
15.5
作者：
Fuks G;Elgart M;Amir A;Zeisel A;Turnbaugh PJ;Soen Y;Shental N
通讯作者：
Shental N
影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
64.5
作者：
Chung H;Pamp SJ;Hill JA;Surana NK;Edelman SM;Troy EB;Reading NC;Villablanca EJ;Wang S;Mora JR;Umesaki Y;Mathis D;Benoist C;Relman DA;Kasper DL
通讯作者：
Kasper DL
影响因子：
17.1
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通讯作者：
Versalovic J
影响因子：
9.8
作者：
Funkhouser LJ;Bordenstein SR
通讯作者：
Bordenstein SR