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Infections at the maternal–fetal interface: an overview of pathogenesis and defence

Nature Reviews Microbiology volume 20, pages 67–82 (2022)Cite this article

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Abstract

Infections are a major threat to human reproductive health, and infections in pregnancy can cause prematurity or stillbirth, or can be vertically transmitted to the fetus leading to congenital infection and severe disease. The acronym ‘TORCH’ (Toxoplasma gondii, other, rubella virus, cytomegalovirus, herpes simplex virus) refers to pathogens directly associated with the development of congenital disease and includes diverse bacteria, viruses and parasites. The placenta restricts vertical transmission during pregnancy and has evolved robust mechanisms of microbial defence. However, microorganisms that cause congenital disease have likely evolved diverse mechanisms to bypass these defences. In this Review, we discuss how TORCH pathogens access the intra-amniotic space and overcome the placental defences that protect against microbial vertical transmission.

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Fig. 1: Routes of transmission across the placenta and consequences of infection.
Fig. 2: Structure and cellular composition of the maternal–fetal interface.
Fig. 3: Placental defences against pathogens.
Fig. 4: Possible mechanisms of vertical transmission.
Fig. 5: Placental malaria in endemic areas.

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Acknowledgements

The authors’ work on the placenta is supported by NIH AI145828 (C.B.C.) and a Magee Women’s Research Institute Clinical Trainee Research Award 4032 (C.J.M.). Additionally, C.J.M. is supported by K12 HD000849 awarded to the Reproductive Scientist Development Program. The authors apologize to any authors whose work was not included owing to space limitations.

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Authors and Affiliations

  1. Division of Maternal–Fetal Medicine, Division of Reproductive Infectious Disease, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine and the Magee Womens Research Institute, Pittsburgh, PA, USA

    Christina J. Megli

  2. Department of Molecular Genetics and Microbiology and the Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA

    Carolyn B. Coyne

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  1. Christina J. Megli
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Glossary

Granulysins

Antimicrobial peptides that can cause pores in bacterial cell walls, leading to cell death.

Osteochondritis

Inflammation of the cartilage.

Hydrops

The presence of excess fluid in two or more fetal body compartments, associated with severe perinatal morbidity and death.

Pyelonephritis

Inflammation and infection of the kidney.

Chorioamnionitis

Inflammation of the fetal membranes, classically associated with bacterial infection.

Intrapartum prophylaxis

The process of giving antibiotics, typically penicillins, to individuals in labour for treatment of group B Streptococcus colonization.

Pericytes

Specialized connective cells of mesenchymal origin that classically surround endothelial cells in blood vessels.

Aplasia cutis

A condition in which parts of the skin are missing.

Ventriculomegaly

A condition in which the brain ventricles are abnormally large.

Microcephaly

An abnormally small circumference.

Chorioretinitis

Inflammation of the choroid surrounding the retina of the eye.

Atrophy

Degenerative and small.

Hydrocephalus

Central nervous system abnormality from pathological ventriculomegaly with excess fluid in the brain causing compression of brain parenchyma and requiring treatment.

Lissencephaly

A brain malformation associated with severe developmental delay in which gyration of the brain is absent.

Apgar score

A score assigned to neonates associated with neonatal health after birth. Infants are scored 0–2 points on muscle tone, skin colour, respiratory effort, pulse and reflex irritability at 1, 5 and 10 min after birth.

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Megli, C.J., Coyne, C.B. Infections at the maternal–fetal interface: an overview of pathogenesis and defence. Nat Rev Microbiol 20, 67–82 (2022). https://doi.org/10.1038/s41579-021-00610-y

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