Microbial exposure during early human development primes fetal immune cells

Summary

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 14 ^th weeks fetal gut lumen. These findings indicate selective presence of live microbes in fetal organs during the 2 ^nd trimester of gestation and have broader implications toward the establishment of immune competency and priming before birth.

Graphical abstract

Highlights

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  Human fetuses in 2 ^nd trimester show T cell diversity with effector-memory phenotype

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  Fetal organs show diverse bacterial genera that can be cultured and propagated

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  Bacterial structures with mucin-like threads are visualized in 14-weeks EGA fetal gut

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  Fetal bacteria induce syngeneic memory T cell activation in fetal mLN T cells

Abstract

Analysis of human fetal tissues and the placenta in the 2 ^nd 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.