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  • Microbial exposure during early human development primes fetal immune cells.

Microbial exposure during early human development primes fetal immune cells.

Cell (2021-06-03)
Archita Mishra, Ghee Chuan Lai, Leong Jing Yao, Thet Tun Aung, Noam Shental, Aviva Rotter-Maskowitz, Edwin Shepherdson, Gurmit Singh Naranjan Singh, Rhea Pai, Adhika Shanti, Regina Men Men Wong, Andrea Lee, Costerwell Khyriem, Charles Antoine Dutertre, Svetoslav Chakarov, K G Srinivasan, Nurhidaya Binte Shadan, Xiao-Meng Zhang, Shabnam Khalilnezhad, Fabien Cottier, Alrina Shin Min Tan, Gillian Low, Phyllis Chen, Yiping Fan, Pei Xiang Hor, Avery Khoo May Lee, Mahesh Choolani, David Vermijlen, Ankur Sharma, Garold Fuks, Ravid Straussman, Norman Pavelka, Benoit Malleret, Naomi McGovern, Salvatore Albani, Jerry Kok Yen Chan, Florent Ginhoux
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 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Xylenes, histological grade
Sigma-Aldrich
Human Serum, from human male AB plasma, USA origin, sterile-filtered
Sigma-Aldrich
5R-PLEX beads, for PCR purification