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The unique immunological and microbial aspects of pregnancy

Key Points

  • The immunology of pregnancy has been considered as a host–graft response characterized by immune suppression and consequently a period of increased risk of bacterial and viral infection.

  • However, accumulating evidence suggests that pregnancy is a more complex immunological condition, and thus a reassessment of many the immunological processes evaluated during pregnancy is required.

  • Whereas a successful organ transplant requires constant immunosuppression, a successful pregnancy requires a robust, dynamic and responsive immune system.

  • Embryo implantation and trophoblast invasion require a local inflammatory environment that promotes cell clearance, angiogenesis, cell growth and tolerance.

  • Pregnancy complications, such as preterm birth, are often polymicrobial in nature and can involve viral infections that sensitize the pregnant mother to subsequent bacterial infections.

  • Interferon-β is a crucial immune modulator during pregnancy; it protects the fetus against viral infections and contributes to the process of immune regulation at the maternal–fetal interface.

  • The immune response associated with placental viral infections can affect maternal and fetal survival.

  • Maternal inflammation due to viral or bacterial infections has detrimental consequences for fetal development.

Abstract

The comparison of the immunological state of pregnancy to an immunosuppressed host–graft model continues to lead research and clinical practice to ill-defined approaches. This Review discusses recent evidence that supports the idea that immunological responses at the receptive maternal–fetal interface are not simply suppressed but are instead highly dynamic. We discuss the crucial role of trophoblast cells in shaping not only the way in which immune cells respond to the invading blastocyst but also how they collectively react to external stimuli. We also discuss the role of the microbiota in promoting a tolerogenic maternal immune system and highlight how subclinical viral infections can disrupt this status quo, leading to pregnancy complications.

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Figure 1: Immune cells at the maternal–fetal interface.
Figure 2: A comparison of antigen presentation in transplants, tumours and early pregnancy.
Figure 3: Similarities between micrometastasis and blastocyst implantation.
Figure 4: The three immunological stages of pregnancy.
Figure 5: The role of dendritic cells in blastocyst implantation.
Figure 6: Trophoblast-mediated immune regulation.

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Mouse gammaherpesvirus 68

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Glossary

Myometrium

The middle layer of the uterine wall. It comprises mainly smooth muscle cells (also known as uterine myocytes) and supporting stromal and vascular tissue, and its main function is to induce uterine contractions during labour.

Chorioamnionitis

Inflammation of the fetal membranes (amnion and chorion) due to a bacterial infection. It typically results from bacteria ascending into the uterus from the vagina and is most often associated with prolonged labour.

Maternal immune activation

A state in which maternal serum cytokine concentrations are elevated. This state is thought to cause neurological deficits in the offspring.

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Mor, G., Aldo, P. & Alvero, A. The unique immunological and microbial aspects of pregnancy. Nat Rev Immunol 17, 469–482 (2017). https://doi.org/10.1038/nri.2017.64

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