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Mild maternal infection promotes immunity and inflammation in offspring

BETHESDA, MD (US), August 2021 — During pregnancy, mild infections in the mother can have permanent and tissue-specific impacts on offspring immunity, according to a new study in mice. The findings reveal that although the fetus can co-opt maternal infection to promote heightened immunity to gut infection, it may do so at the cost of a long-lasting predisposition to inflammatory disorders in offspring.

A growing body of evidence suggests that the immune system begins to develop in utero and is greatly affected by maternal immune status during pregnancy. While pregnancy is often associated with immune suppression, it remains unknown how every-day infections – such as mild urinary tract, respiratory or food-borne infections – that remain undiagnosed and often self-resolve in the mother can influence the offspring’s immunity.

To evaluate the impact of maternal infection on offspring immunity, Ai Ing Lim, postdoctoral research fellow at the National Institute of Allergy and Infectious Diseases, National Institutes of Health,

 and colleagues infected pregnant mice with a specific strain of the common food-borne pathogen Yersinia pseudotuberculosis, which causes a mild and transient infection. However, while the short-lived infection was restricted to the mother, Dr. Lim and the research team observed elevated levels of intestinal T helper 17 (Th17) cells in the offspring, which persisted into adulthood. They found that enriched levels of the pro-inflammatory cytokine interleukin-6 (IL-6) produced by the mother in response to infection resulted in epigenetic changes to the fetal intestinal epithelium stem cells during in utero development. While these offspring showed enhanced protective immunity to gut infection, they also exhibited higher susceptibility to intestinal inflammatory disease, like colitis.

“The past few decades have seen a marked increase in the incidence of inflammatory disorders in children, including asthma, allergies and behavioral deficits driven in part by neuroinflammation,” wrote Mohammed Amir and Melody Zeng in a related Perspective. “Future work should address whether and how immune imprinting in utero may underlie the predisposition to inflammatory disorders.”


The direct response of fetal intestinal epithelial cells to IL-6 during maternal infection confers an enduring epigenetic memory to adult intestinal epithelial stem cells. As such, offspring epithelial cells exhibit enhanced reactivity toward the microbiota and heightened ability to control oral infection. However, these responses come at the cost of greater predisposition to gut inflammation. Image courtesy of Ai Ing Lim/Science.

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DOI: 10.1126/science.abf3002