1. Microbial exposure during early human development primes fetal immune cells.
- Author
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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, and Ginhoux F
- Subjects
- Adult, Bacteria genetics, Bacteria ultrastructure, Cell Proliferation, Dendritic Cells metabolism, Female, Fetus ultrastructure, Gastrointestinal Tract embryology, Gastrointestinal Tract ultrastructure, Humans, Immunologic Memory, Lymphocyte Activation immunology, Microbial Viability, Pregnancy, Pregnancy Trimester, Second, RNA, Bacterial genetics, RNA, Ribosomal, 16S genetics, Reproducibility of Results, T-Lymphocytes cytology, Bacteria metabolism, Embryonic Development, Fetus cytology, Fetus microbiology, Leukocytes cytology
- Abstract
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 2
nd 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., Competing Interests: Declaration of interests The authors declare no competing interests., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
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