Microbial exposure during early human development primes fetal immune cells

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Mishra, Archita 
Lai, Ghee Chuan 
Yao, Leong Jing 
Aung, Thet Tun 
Shental, Noam 

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 towards 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 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 visualised discrete localisation of bacteria-like structures and eubacterial-RNA within 14th week fetal gut lumen. These findings indicate selective presence of live-microbes in fetal organs during 2nd trimester of gestation and have broader implications towards establishment of immune competency and priming before birth

Tem, Treg, bacteria, fetal Development, fetal immunity, immune memory, immune priming, microbes, microbiome, Adult, Bacteria, Cell Proliferation, Dendritic Cells, Embryonic Development, Female, Fetus, Gastrointestinal Tract, Humans, Immunologic Memory, Leukocytes, Lymphocyte Activation, Microbial Viability, Pregnancy, Pregnancy Trimester, Second, RNA, Bacterial, RNA, Ribosomal, 16S, Reproducibility of Results, T-Lymphocytes
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Wellcome Trust (204464/Z/16/Z)