Microbial exposure during early human development primes fetal immune cells

Cell. 2021 Jun 24;184(13):3394-3409.e20. doi: 10.1016/j.cell.2021.04.039. Epub 2021 Jun 1.


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.

Keywords: Tem; Treg; bacteria; fetal Development; fetal immunity; immune memory; immune priming; microbes; microbiome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bacteria / genetics
  • Bacteria / metabolism*
  • Bacteria / ultrastructure
  • Cell Proliferation
  • Dendritic Cells / metabolism
  • Embryonic Development*
  • Female
  • Fetus / cytology*
  • Fetus / microbiology*
  • Fetus / ultrastructure
  • Gastrointestinal Tract / embryology
  • Gastrointestinal Tract / ultrastructure
  • Humans
  • Immunologic Memory
  • Leukocytes / cytology*
  • Lymphocyte Activation / immunology
  • Microbial Viability
  • Pregnancy
  • Pregnancy Trimester, Second
  • RNA, Bacterial / genetics
  • RNA, Ribosomal, 16S / genetics
  • Reproducibility of Results
  • T-Lymphocytes / cytology


  • RNA, Bacterial
  • RNA, Ribosomal, 16S