Prenatal maternal infection promotes tissue-specific immunity and inflammation in offspring.

TitlePrenatal maternal infection promotes tissue-specific immunity and inflammation in offspring.
Publication TypeJournal Article
Year of Publication2021
AuthorsLim, AIng, McFadden, T, Link, VM, Han, S-J, Karlsson, R-M, Stacy, A, Farley, TK, Lima-Junior, DS, Harrison, OJ, Desai, JV, Lionakis, MS, Shih, H-Y, Cameron, HA, Belkaid, Y
JournalScience
Volume373
Issue6558
Date Published2021/08/27
ISSN1095-9203
KeywordsAnimals, Candidiasis, Chromatin, Colitis, Epigenesis, Genetic, Epigenome, Female, Fetal Development, Gastrointestinal Microbiome, Immunity, Interleukin-6, Intestinal Mucosa, Intestines, Mice, Pregnancy, Pregnancy Complications, Infectious, Prenatal Exposure Delayed Effects, Salmonella Infections, Animal, Stem Cells, T-Lymphocyte Subsets, Th17 Cells, Yersinia pseudotuberculosis Infections
Abstract

The immune system has evolved in the face of microbial exposure. How maternal infection experienced at distinct developmental stages shapes the offspring immune system remains poorly understood. Here, we show that during pregnancy, maternally restricted infection can have permanent and tissue-specific impacts on offspring immunity. Mechanistically, maternal interleukin-6 produced in response to infection can directly impose epigenetic changes on fetal intestinal epithelial stem cells, leading to long-lasting impacts on intestinal immune homeostasis. As a result, offspring of previously infected dams develop enhanced protective immunity to gut infection and increased inflammation in the context of colitis. Thus, maternal infection can be coopted by the fetus to promote long-term, tissue-specific fitness, a phenomenon that may come at the cost of predisposition to inflammatory disorders.

DOI10.1126/science.abf3002
Alternate JournalScience
PubMed ID34446580
Grant ListZIA AI001115 / ImNIH / Intramural NIH HHS / United States
ZIA AI001132 / ImNIH / Intramural NIH HHS / United States
ZIA MH002784 / ImNIH / Intramural NIH HHS / United States
ZIA AI001175 / ImNIH / Intramural NIH HHS / United States