bims-reprim 2021-03-21 papers

Issue of 2021–03–21
two papers selected by
Iva Filipovic, Karolinska Institutet

Hum Immunol. 2021 Mar 11. pii: S0198-8859(21)00063-X. [Epub ahead of print]

Contribution of macrophages to fetomaternal immunological tolerance.

The semi-allogeneic fetus develops in a uniquely immune tolerant environment within the uterus. For successful pregnancy, both the innate and adaptive immune systems must favor acceptance of the fetal allograft. Macrophages are the second most abundant immune cells after natural killer (NK) cells in the decidua. In coordination with decidual NK cells and dendritic cells, macrophages aid in implantation, vascular remodeling, placental development, immune tolerance to placental cells, and maintenance of tissue homeostasis at the maternal-fetal interface. Decidual macrophages show the classical activated (M1) and alternatively activated (M2) phenotypes under the influence of the local milieu of growth factors and cytokines, and appropriate temporal regulation of the M1/M2 switch is vital for successful pregnancy. Disturbances in the mechanisms that control the M1/M2 balance and associated functions during pregnancy can trigger a spectrum of pregnancy complications ranging from preeclampsia and fetal growth restriction to preterm delivery. This review addresses various mechanisms of tolerance, focusing on the basic biology of macrophages, their plasticity and polarization, and their protective roles at the immune-privileged maternal-fetal interface, including direct and indirect roles in promoting fetomaternal immune tolerance.

Keywords: Decidua; Immune tolerance; Macrophages; Maternal-fetal interface; Placenta; Pregnancy

DOI: https://doi.org/10.1016/j.humimm.2021.02.013

Placenta. 2021 Mar 01. pii: S0143-4004(21)00073-4. [Epub ahead of print]107 24-30

Chronic villitis of unknown etiology: Investigations into viral pathogenesis.

Linda M Ernst, Crystal Bockoven, Alexa Freedman, Vivien Wang, Matthew Pellerite, Todd N Wylie, Kristine M Wylie.

INTRODUCTION: Chronic villitis of unknown etiology (VUE) is a chronic inflammatory lesion of third trimester placenta, which contributes to major adverse obstetric outcomes. However, the inciting factors and mechanisms by which VUE contributes to adverse outcomes are poorly understood. This limits our ability to develop preventions or interventions. Our goals were to determine whether viruses can be detected in placental tissues with VUE and to determine whether gene expression profiles support an antiviral response.
METHODS: We extracted RNA and DNA from 20 placentas with high-grade chronic villitis and 20 control placentas without inflammation. Viruses were assessed using ViroCap viral nucleic acid enrichment coupled with metagenomic sequencing. RNA sequencing was used to evaluate the inflammatory gene expression profiles in each placenta.
RESULTS: We detected at least 1 virus in 50% of the samples tested. We found that herpesviruses, were found more frequently in cases compared with controls (P = 0.01). Antiviral pathways, including defense response to virus, interferon gamma response, and IFN alpha/beta response, were upregulated in cases. We observed two clusters of gene expression profiles in the VUE cases, suggesting multiple inflammatory profiles are associated with VUE.
DISCUSSION: These data support a viral etiology for some cases of VUE. Furthermore, gene expression profiles suggest the possibility of more than one cause or manifestation of VUE. Viral mechanisms should be explored as potential targets for prevention or intervention in VUE.

Keywords: Chronic villitis of unknown etiology; Herpesviruses; Placenta; Virome

DOI: https://doi.org/10.1016/j.placenta.2021.02.020