ACE2 Is Expressed in Immune Cells That Infiltrate the Placenta in Infection-Associated Preterm Birth
COVID-19 is associated with increased incidence of preterm birth (PTB). We assessed pathways by which SARS-CoV-2 could access the placenta. Placentae, from PTB with or without chorioamnionitis (ChA), or from term pregnancies (<i>n</i> = 12/13/group) were collected. Peripheral blood was c...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-07-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/10/7/1724 |
| _version_ | 1797527395903733760 |
|---|---|
| author | Phetcharawan Lye Caroline E. Dunk Jianhong Zhang Yanxing Wei Jittanan Nakpu Hirotaka Hamada Guinever E. Imperio Enrrico Bloise Stephen G. Matthews Stephen J. Lye |
| author_facet | Phetcharawan Lye Caroline E. Dunk Jianhong Zhang Yanxing Wei Jittanan Nakpu Hirotaka Hamada Guinever E. Imperio Enrrico Bloise Stephen G. Matthews Stephen J. Lye |
| author_sort | Phetcharawan Lye |
| collection | DOAJ |
| description | COVID-19 is associated with increased incidence of preterm birth (PTB). We assessed pathways by which SARS-CoV-2 could access the placenta. Placentae, from PTB with or without chorioamnionitis (ChA), or from term pregnancies (<i>n</i> = 12/13/group) were collected. Peripheral blood was collected from healthy pregnant women (<i>n</i> = 6). Second trimester placental explants (16–20 weeks, <i>n</i> = 5/group) were treated with lipopolysaccharide (LPS, to mimic bacterial infection) and ACE2, CCL2, IL-6/8 and TNFα mRNA was assessed. ChA-placentae exhibited increased <i>ACE2</i> and <i>CCL2</i> mRNA expression (<i>p</i> < 0.05). LPS increased cytokine and <i>ACE2</i> mRNA in placental explants. Placental ACE2 protein localized to syncytiotrophoblast, fetal endothelium, extravillous trophoblast and in immune cells-subsets (M1/M2 macrophage and neutrophils) within the villous stroma. Significantly increased numbers of M1 macrophage and neutrophils were present in the ChA-placenta (<i>p</i> < 0.001). Subsets of peripheral immune cells from pregnant women express the ACE2 mRNA and protein. A greater fraction of granulocytes was positive for ACE2 protein expression compared to lymphocytes or monocytes. These data suggest that in pregnancies complicated by ChA, ACE2 positive immune cells in the maternal circulation have the potential to traffic SARS-CoV-2 virus to the placenta and increase the risk of vertical transmission to the placenta/fetus. |
| first_indexed | 2024-03-10T09:43:17Z |
| format | Article |
| id | doaj.art-9a7b9d9d8a0b4c5f904538ce9d226ee4 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T09:43:17Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-9a7b9d9d8a0b4c5f904538ce9d226ee42023-11-22T03:29:01ZengMDPI AGCells2073-44092021-07-01107172410.3390/cells10071724ACE2 Is Expressed in Immune Cells That Infiltrate the Placenta in Infection-Associated Preterm BirthPhetcharawan Lye0Caroline E. Dunk1Jianhong Zhang2Yanxing Wei3Jittanan Nakpu4Hirotaka Hamada5Guinever E. Imperio6Enrrico Bloise7Stephen G. Matthews8Stephen J. Lye9Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, CanadaLunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON M5G 1X5, CanadaLunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON M5G 1X5, CanadaLunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON M5G 1X5, CanadaLunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON M5G 1X5, CanadaDepartment of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, CanadaLunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON M5G 1X5, CanadaDepartment of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, CanadaDepartment of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, CanadaDepartment of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, CanadaCOVID-19 is associated with increased incidence of preterm birth (PTB). We assessed pathways by which SARS-CoV-2 could access the placenta. Placentae, from PTB with or without chorioamnionitis (ChA), or from term pregnancies (<i>n</i> = 12/13/group) were collected. Peripheral blood was collected from healthy pregnant women (<i>n</i> = 6). Second trimester placental explants (16–20 weeks, <i>n</i> = 5/group) were treated with lipopolysaccharide (LPS, to mimic bacterial infection) and ACE2, CCL2, IL-6/8 and TNFα mRNA was assessed. ChA-placentae exhibited increased <i>ACE2</i> and <i>CCL2</i> mRNA expression (<i>p</i> < 0.05). LPS increased cytokine and <i>ACE2</i> mRNA in placental explants. Placental ACE2 protein localized to syncytiotrophoblast, fetal endothelium, extravillous trophoblast and in immune cells-subsets (M1/M2 macrophage and neutrophils) within the villous stroma. Significantly increased numbers of M1 macrophage and neutrophils were present in the ChA-placenta (<i>p</i> < 0.001). Subsets of peripheral immune cells from pregnant women express the ACE2 mRNA and protein. A greater fraction of granulocytes was positive for ACE2 protein expression compared to lymphocytes or monocytes. These data suggest that in pregnancies complicated by ChA, ACE2 positive immune cells in the maternal circulation have the potential to traffic SARS-CoV-2 virus to the placenta and increase the risk of vertical transmission to the placenta/fetus.https://www.mdpi.com/2073-4409/10/7/1724SARS-CoV-2COVID-19ACE2chorioamnionitispreterm birthM1 |
| spellingShingle | Phetcharawan Lye Caroline E. Dunk Jianhong Zhang Yanxing Wei Jittanan Nakpu Hirotaka Hamada Guinever E. Imperio Enrrico Bloise Stephen G. Matthews Stephen J. Lye ACE2 Is Expressed in Immune Cells That Infiltrate the Placenta in Infection-Associated Preterm Birth Cells SARS-CoV-2 COVID-19 ACE2 chorioamnionitis preterm birth M1 |
| title | ACE2 Is Expressed in Immune Cells That Infiltrate the Placenta in Infection-Associated Preterm Birth |
| title_full | ACE2 Is Expressed in Immune Cells That Infiltrate the Placenta in Infection-Associated Preterm Birth |
| title_fullStr | ACE2 Is Expressed in Immune Cells That Infiltrate the Placenta in Infection-Associated Preterm Birth |
| title_full_unstemmed | ACE2 Is Expressed in Immune Cells That Infiltrate the Placenta in Infection-Associated Preterm Birth |
| title_short | ACE2 Is Expressed in Immune Cells That Infiltrate the Placenta in Infection-Associated Preterm Birth |
| title_sort | ace2 is expressed in immune cells that infiltrate the placenta in infection associated preterm birth |
| topic | SARS-CoV-2 COVID-19 ACE2 chorioamnionitis preterm birth M1 |
| url | https://www.mdpi.com/2073-4409/10/7/1724 |
| work_keys_str_mv | AT phetcharawanlye ace2isexpressedinimmunecellsthatinfiltratetheplacentaininfectionassociatedpretermbirth AT carolineedunk ace2isexpressedinimmunecellsthatinfiltratetheplacentaininfectionassociatedpretermbirth AT jianhongzhang ace2isexpressedinimmunecellsthatinfiltratetheplacentaininfectionassociatedpretermbirth AT yanxingwei ace2isexpressedinimmunecellsthatinfiltratetheplacentaininfectionassociatedpretermbirth AT jittanannakpu ace2isexpressedinimmunecellsthatinfiltratetheplacentaininfectionassociatedpretermbirth AT hirotakahamada ace2isexpressedinimmunecellsthatinfiltratetheplacentaininfectionassociatedpretermbirth AT guinevereimperio ace2isexpressedinimmunecellsthatinfiltratetheplacentaininfectionassociatedpretermbirth AT enrricobloise ace2isexpressedinimmunecellsthatinfiltratetheplacentaininfectionassociatedpretermbirth AT stephengmatthews ace2isexpressedinimmunecellsthatinfiltratetheplacentaininfectionassociatedpretermbirth AT stephenjlye ace2isexpressedinimmunecellsthatinfiltratetheplacentaininfectionassociatedpretermbirth |