Pregnancy Induces an Immunological Memory Characterized by Maternal Immune Alterations Through Specific Genes Methylation.

Xiaobo Huang,Anthony Maxwell,Zhinan Yin,Li Wu,Aihua Liao,Jiahui Ding,Sijia Zhao,Liling Wang,Liping Liu,Hengwen Yang,Si Chen,Gil Mor,Hong Liu

doi:10.3389/fimmu.2021.686676

Abstract

During pregnancy, the maternal immune system undergoes major adaptive modifications that are necessary for the acceptance and protection of the fetus. It has been postulated that these modifications are temporary and limited to the time of pregnancy. Growing evidence suggests that pregnancy has a long-term impact on maternal health, especially among women with pregnancy complications, such as preeclampsia (PE). In addition, the presence of multiple immunological-associated changes in women that remain long after delivery has been reported. To explain these long-term modifications, we hypothesized that pregnancy induces long-term immunological memory with effects on maternal well-being. To test this hypothesis, we evaluated the immunological phenotype of circulating immune cells in women at least 1 year after a normal pregnancy and after pregnancy complicated by PE. Using multiparameter flow cytometry (FCM) and whole-genome bisulfite sequencing (WGBS), we demonstrate that pregnancy has a long-term effect on the maternal immune cell populations and that this effect differs between normal pregnancy and pregnancy complicated by PE; furthermore, these modifications are due to changes in the maternal methylation status of genes that are associated with T cell and NK cell differentiation and function. We propose the existence of an “immunological memory of pregnancy (IMOP)” as an evolutionary advantage for the success of future pregnancies and the proper adaptation to the microchimeric status established during pregnancy. Our findings demonstrate that the type of immune cell populations modified during pregnancy may have an impact on subsequent pregnancy and future maternal health.

Highlights

Pregnancy is a period when the female body undergoes major transformations and physiological adaptations that are necessary to sustain and protect the growing fetus [1]
Blood samples collected from each woman were analyzed with multiparameter flow cytometry (FCM) to assess 63 immunological parameters, including the T cell, natural killer (NK) cell and gd T cell subsets
We described for the first time the long-term effect of pregnancy on the maternal immune system and provide the evidence for the existence of a long-term “immunological memory of pregnancy (IMOP)”

Summary

Introduction

Pregnancy is a period when the female body undergoes major transformations and physiological adaptations that are necessary to sustain and protect the growing fetus [1] These changes begin after conception and will affect several different organ systems in the mother, including the endocrine, cardiac, metabolic and immune systems [2]. The number of fetal cells in maternal tissue increases with the gestation, and these cells can still be found years after delivery [8] This microchimeric state requires the continued maintenance of adaptive changes in the maternal immune system in order to facilitate the long-term presence of the fetal cells

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