Infection During Pregnancy ‘Imprints’ Immunity, and Inflammation, on Offspring

Infection During Pregnancy ‘Imprints’ Immunity, and Inflammation, on Offspring
Mouse Study Explores Microbial and Environmental Changes in Immune Development

Mice infected with a foodborne bacterium during pregnancy generated an immune response in the gut that protected the mother and imprinted that protective response in the developing offspring, NIAID scientists show in a new study published in Science. The maternal immune response to the infection, they reveal, uses protein signals that teach the developing fetal cells to remember the infection.

The story isn’t all rosy though: The researchers also discovered that those signaling proteins, interleukin 6 (IL-6), also make the developing fetus more prone to inflammatory disorders, such as colitis.

The findings come from the laboratory of NIAID intramural investigator Dr. Yasmine Belkaid. Collaborators include other NIAID intramural groups as well as the National Institute of Mental Health; National Institute of General Medical Sciences; National Eye Institute; and University of Oxford.

Their study not only informs how a host immune system can imprint immunity on a developing fetus, but also raises new questions of whether scientists can use immune components, such as IL-6, to prime developing cells to fight disease.

Scientists conducted the study by infecting pregnant mice with a weakened strain of Yersinia pseudotuberculosis, a bacterium consumed in foods. The dams developed mild disease, cleared the infection in about a week, and then gave birth.

When the offspring developed into adults, the scientists discovered that, compared to control animals, they had elevated levels of helper immune cells known as Th17 in the small intestine. They also determined that the mice had acquired the ability to develop increased T helper immune responses during their development in the uterus of the infected dam.

The scientists found that IL-6 was specifically increased in infected dams, and injection of pregnant mice with IL-6 alone showed elevated Th17 cells and enhanced responses to infection in the offspring.

“Our findings support the idea that increased levels of IL-6, elicited by transient infection during pregnancy, alter offspring intestinal immunity,” the scientists say. “… pregnancy represents a critical stage for tissue-specific immune education of the offspring.” They add, however, that “heightened immunity can also come at the cost of increased susceptibility to inflammatory disorders.”

The researchers plan additional studies of the maternal-fetal relationship and whether microbial and environmental changes – in animal models and people – can shift immune development from protective to inflammatory.

Reference: A. Lim, et al. Prenatal maternal infection promotes tissue-specific immunity and inflammation in offspring. Science. DOI: 10.1126/science.abf3002 (2021).