Maternal infection promotes offspring tissue-specific immune fitness

Lim et al (BioRxiv). DOI: 10.1101/2021.01.13.426542

 

Keywords

  • Maternal infection

  • Th-17 cells

  • Microbiome

 

Main Findings

In this preprint, Lim and colleagues dissect the role of mild or asymptomatic infections during pregnancy in training offspring immune responses. Upon infecting pregnant dams with yopM, an attenuated strain of Yersinia pseudotuberculosis, the authors found that adult offspring of infected mothers exhibited a substantial increase in intestinal Th-17 cell abundance compared to controls. Mechanistically, yopM infection induced maternal production of IL-6, which epigenetically altered fetal epithelial cells to create an intestinal microenvironment conducive to Th-17 cell differentiation.  Administration of IL-6 alone to pregnant mothers recapitulated this affect.  Moreover, the increased abundance of Th-17 cells protected offspring of infected mothers from lethal infection with the intestinal pathogen Salmonella enterica subsp. Enterica serovar Typhimurium.

Highlights

  • Defined a novel mechanism of maternal infection imprinting a tissue-specific immune response in adult offspring.

  • Used a reductionist model to prove that maternal IL-6 epigenetically modifies fetal intestinal epithelial cells with long-term consequences into adulthood.

Significance/Novelty

Most studies of maternal infection focus on pathogens with catastrophic consequences for offspring, such as Zika virus or cytomegalovirus. Here, Lim et al describe how common, mild infections during pregnancy profoundly influence the immune fitness of adult offspring. Future studies are needed to clarify if these findings are translatable to humans and to determine the breadth of pathogens that can induce this Th-17 cell-driven immune protection.