bims-reprim 2021-11-14 papers

Issue of 2021‒11‒14
six papers selected by
Iva Filipovic
Karolinska Institutet

Front Immunol. 2021 ;12 758281

Crosstalk Between Trophoblast and Macrophage at the Maternal-Fetal Interface: Current Status and Future Perspectives.

Jinli Ding, Yan Zhang, Xiaopeng Cai, Lianghui Diao, Chaogang Yang, Jing Yang.

The immune tolerance microenvironment is crucial for the establishment and maintenance of pregnancy at the maternal-fetal interface. The maternal-fetal interface is a complex system containing various cells, including lymphocytes, decidual stromal cells, and trophoblasts. Macrophages are the second-largest leukocytes at the maternal-fetal interface, which has been demonstrated to play essential roles in remodeling spiral arteries, maintaining maternal-fetal immune tolerance, and regulating trophoblast's biological behaviors. Many researchers, including us, have conducted a series of studies on the crosstalk between macrophages and trophoblasts at the maternal-fetal interface: on the one hand, macrophages can affect the invasion and migration of trophoblasts; on the other hand, trophoblasts can regulate macrophage polarization and influence the state of the maternal-fetal immune microenvironment. In this review, we systemically introduce the functions of macrophages and trophoblasts and the cell-cell interaction between them for the establishment and maintenance of pregnancy. Advances in this area will further accelerate the basic research and clinical translation of reproductive medicine.

Keywords: immune tolerance; macrophage; maternal-fetal interface; pregnancy; trophoblast

DOI: https://doi.org/10.3389/fimmu.2021.758281

Curr Opin Immunol. 2021 Nov 09. pii: S0952-7915(21)00140-0. [Epub ahead of print]74 60-67

Innate immune defenses at the maternal-fetal interface.

Eleanor C Semmes, Carolyn B Coyne.

The human maternal-fetal interface is an immunologically complex environment that must balance the divergent demands of tolerance towards the developing fetus with anti-pathogen defense. The innate immune responses at the maternal-fetal interface that function in anti-microbial defense have been understudied to-date and how 'TORCH' pathogens evade maternal innate immunity to infect the fetus remains poorly understood. Herein, we discuss how newly described decidual innate lymphoid cells and maternal placenta-associated macrophage subsets may be involved in anti-pathogen defense. Moreover, we outline recent advances in our understanding of how placental trophoblasts and fetal-derived macrophages (Hofbauer cells) function in anti-microbial defense. In summary, we highlight current gaps in knowledge and describe novel experimental models of the human decidua and placenta that are poised to advance our knowledge of innate immune defenses at the maternal-fetal interface.

DOI: https://doi.org/10.1016/j.coi.2021.10.007

Cell Rep Med. 2021 Nov 04. 100456

SARS-CoV-2 can infect and propagate in human placenta explants.

Amal Fahmi, Melanie Brügger, Thomas Démoulins, Beatrice Zumkehr, Blandina I Oliveira Esteves, Lisamaria Bracher, Carlos Wotzkow, Fabian Blank, Volker Thiel, David Baud, Marco P Alves.

The ongoing SARS-CoV-2 pandemic continues to lead to high morbidity and mortality. During pregnancy, severe maternal and neonatal outcomes and placental pathological changes have been described. We evaluate SARS-CoV-2 infection at the maternal-fetal interface using precision-cut slices (PCSs) of human placenta. Remarkably, exposure of placenta PCSs to SARS-CoV-2 leads to a full replication cycle with infectious virus release. Moreover, the susceptibility of placental tissue to SARS-CoV-2 replication relates to the expression levels of ACE2. Viral proteins and/or RNA are detected in syncytiotrophoblast, cytotrophoblasts, villous stroma, and possibly Hofbauer cells. While SARS-CoV-2 infection of placenta PCSs does not cause a detectable cytotoxicity nor a pro-inflammatory cytokine response, an upregulation of one order of magnitude of interferon type III transcripts is measured. In conclusion, our data demonstrate the capacity of SARS-CoV-2 to infect and propagate in human placenta and constitute a basis for further investigation of SARS-CoV-2 biology at the maternal-fetal interface.

Keywords: COVID-19; SARS-CoV-2; coronavirus; pandemic; placenta; pregnancy; vertical transmission

DOI: https://doi.org/10.1016/j.xcrm.2021.100456

Front Immunol. 2021 ;12 738962

DNA Methylation and Recurrent Pregnancy Loss: A Mysterious Compass?

Qi Zhou, Yunhe Xiong, Bing Qu, Anyu Bao, Yan Zhang.

Recurrent pregnancy loss (RPL) is a common and severe pathological pregnancy, whose pathogenesis is not fully understood. With the development of epigenetics, the study of DNA methylation, provides a new perspective on the pathogenesis and therapy of RPL. The abnormal DNA methylation of imprinted genes, placenta-specific genes, immune-related genes and sperm DNA may, directly or indirectly, affect embryo implantation, growth and development, leading to the occurrence of RPL. In addition, the unique immune tolerogenic microenvironment formed at the maternal-fetal interface has an irreplaceable effect on the maintenance of pregnancy. In view of these, changes in the cellular components of the maternal-fetal immune microenvironment and the regulation of DNA methylation have attracted a lot of research interest. This review summarizes the research progress of DNA methylation involved in the occurrence of RPL and the regulation of the maternal-fetal immune microenvironment. The review provides insights into the personalized diagnosis and treatment of RPL.

Keywords: DNA methylation; epigenetic; immune; maternal-fetal immune microenvironment; recurrent pregnancy loss (RPL)

DOI: https://doi.org/10.3389/fimmu.2021.738962

Front Immunol. 2021 ;12 771054

The Ontogeny and Function of Placental Macrophages.

Jake R Thomas, Praveena Naidu, Anna Appios, Naomi McGovern.

The placenta is a fetal-derived organ whose function is crucial for both maternal and fetal health. The human placenta contains a population of fetal macrophages termed Hofbauer cells. These macrophages play diverse roles, aiding in placental development, function and defence. The outer layer of the human placenta is formed by syncytiotrophoblast cells, that fuse to form the syncytium. Adhered to the syncytium at sites of damage, on the maternal side of the placenta, is a population of macrophages termed placenta associated maternal macrophages (PAMM1a). Here we discuss recent developments that have led to renewed insight into our understanding of the ontogeny, phenotype and function of placental macrophages. Finally, we discuss how the application of new technologies within placental research are helping us to further understand these cells.

Keywords: development; macrophage; ontogeny; placenta; pregnancy

DOI: https://doi.org/10.3389/fimmu.2021.771054

Am J Perinatol. 2021 Nov 12.

SARS-CoV-2 Antibody Response among Women Infected during Pregnancy.

Ayisha Buckley, Ariana Mills, Keisha Paul, Samantha Raymond, Damondara R Mendu, Chelsea DeBolt, Mitchell Rosenberg, Ania Wajnberg, Libby Szeto, Elizabeth Cochrane, Luciana Vieira, Jill Berkin, Lauren Ferrera, Joanne Stone, Angela Bianco.

OBJECTIVES: Novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) virus has been declared a pandemic by the World Health Organization as of March 11, 2020. Pregnant women naturally have a reduced immune system due to immunological changes and decreased lung capacity due to respiratory adaptations, making them more susceptible to coronavirus complications. Within the Mount Sinai Health system, more than 15,000 deliveries are performed annually. We began to care for pregnant women with known COVID-19 infections in late March of 2020. In early April 2020, a policy was implemented to perform universal COVID-19 testing for all women planning to deliver within the Mount Sinai Health system. We examined the antibody response of postpartum women who delivered at Mount Sinai Hospital with a SARS-CoV-2 infection between the study intervals during March 15, 2020, through April 30, 2020.STUDY DESIGN: This was a prospective observational study examining the immune response of pregnant women who delivered at Mount Sinai Hospital with a polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection. Women with a SARS-CoV-2 infection were contacted via phone to discuss participation in the study. Patients who consented were scheduled for a phlebotomy visit to assess their antibody titer levels to COVID-19. The COVID-19 enzyme-linked immunosorbent assay (ELISA) immunoglobulin (Ig)-G antibody test was used to evaluate the patients' antibody titers. The assay detects IgG antibodies for the detection of IgG seroconversion in patients following a known recent SARS-CoV-2 infection.
RESULTS: A total of 120 patients were identified with a documented SARS-CoV-2 infection who delivered within the prespecified time frame. Of those patients, 25 women agreed to participate and were included. Of them, 64.00% were Caucasian with a mean age of 35 years. The mean body mass index (BMI) was 30 kg/m2 and the majority of patients had commercial insurance (88.00%). The majority of women were asymptomatic for COVID-19 at the time of admission (80.00%) and the average gestational age of delivery and diagnosis of COVID-19 was 39 weeks' gestation. The later the gestational age at the time of diagnosis, the lower the antibody titer response. When examining the interval from diagnosis to antibody titer analysis, patients with the highest titers (2,880) tended to have a shorter interval between their COVID-19 diagnosis and the time at which the titer level was drawn. Patients with symptoms on admission had similar antibody titer levels when compared with women who were asymptomatic.
CONCLUSION: The antibody response among women infected with COVID-19 during pregnancy appears to be greater when the patients are diagnosed at an earlier gestational age.
KEY POINTS: · COVID-19 antibody status appears to be greater when diagnosed at an earlier gestational age.. · Asymptomatic and symptomatic pregnant women had similar antibody responses.. · Patients with the highest titers tended to have a shorter interval between their COVID-19 diagnoses..

DOI: https://doi.org/10.1055/s-0041-1739469