PD-L1 Expression and Characterization of Its Carrier Macrophages in Placentas with Acute and Specifically Post-SARS-CoV-2 Infection

Overview

Journal Histochem Cell Biol

Publisher Springer

Specialties Biochemistry
Cell Biology

Date 2024 Nov 26

PMID 39589546

Authors

Marina C Seefried

Johanna Mittelberger

Manuela Franitza

Fabian Garrido

Carl Mathis Wild

Nina Ditsch

Oleksii Protsepko

Christina Kuhn

Christian Dannecker

Peter Altevogt

Udo Jeschke

Marei Sammar

Affiliations

Soon will be listed here.

Abstract

At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, uncertainties about the virus and its dangers during pregnancy caused great uncertainty and fear, especially among pregnant women. New data suggest an increased risk of obstetric complications, including maternal complications, preterm labor, intrauterine growth restriction, hypertensive disorders, stillbirths, gestational diabetes and risk, of neonatal developmental disorders. In addition, preeclampsia (PE)-like syndromes were also induced by severe COVID-19 infection. Therefore, the aim of this study was to investigate the expression of CD68 and CD163 and PD-L1 on placental tissues from acute covid patients, patients who survived a covid-19 infection and normal term controls that are known to be dysregulated in preeclampsia cases. We examined a total of 60 placentas from women that had given birth to female or male offspring in the University Hospital Augsburg. We investigated ten acute COVID-19 females, ten acute COVID-19 males, ten post-COVID-19 females, ten post-COVID-19 males, ten female term controls, and ten male term controls. Immunohistochemical staining against CD68, CD163, and PD-L1 was performed and the expression of the markers was evaluated with an immunoreactive score (percentage score). Identity of CD163- or PD-L1 expressing cells was analyzed by double immune fluorescence analyses. In opposite to PE, CD163 positive maternal macrophages are significantly upregulated in the decidua of male acute COVID-19 placentas. PD-L1 is significantly upregulated on male acute- and post-COVID-19 decidual immune cells and on male post-COVID-19 extravillous trophoblast cells. Surprisingly the observed effects are related to the fetal gender as they were not observed in female offsprings. Further investigation is necessary to analyze especially the imprinting effect of this infection.

References

Juttukonda L, Wachman E, Boateng J, Jain M, Benarroch Y, Taglauer E . Decidual immune response following COVID-19 during pregnancy varies by timing of maternal SARS-CoV-2 infection. J Reprod Immunol. 2022; 151:103501. PMC: 8867981. DOI: 10.1016/j.jri.2022.103501. View

Schaal N, Hagenbeck C, Helbig M, Wulff V, Marthesheimer S, Fehm T . The influence of being pregnant during the COVID-19 pandemic on birth expectations and antenatal bonding. J Reprod Infant Psychol. 2021; 41(1):15-25. DOI: 10.1080/02646838.2021.1962825. View

Beenen A, Sauerer T, Schaft N, Dorrie J . Beyond Cancer: Regulation and Function of PD-L1 in Health and Immune-Related Diseases. Int J Mol Sci. 2022; 23(15). PMC: 9369208. DOI: 10.3390/ijms23158599. View

Stylianou N, Sebina I, Matigian N, Monkman J, Doehler H, Rohl J . Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies placental dysfunction signatures. Clin Transl Immunology. 2024; 13(2):e1488. PMC: 10846628. DOI: 10.1002/cti2.1488. View

Ambedkar D, Yadav Y, Dubey P, Kumar V, Sharma R, Mishra C . Pregnancy Outcomes in Women With SARS-CoV-2 Infection During the First and Second Waves of the COVID-19 Pandemic in a Tertiary Care Hospital in Ayodhya, Uttar Pradesh, India: A Comparative Study. Cureus. 2023; 15(2):e34969. PMC: 10019494. DOI: 10.7759/cureus.34969. View

Hagenbeck C, Pecks U, Fehm T, Borgmeier F, Schleussner E, Zollkau J . [Pregnancy, birth, and puerperium with SARS-CoV-2 and COVID-19]. Gynakologe. 2020; 53(9):614-623. PMC: 7357434. DOI: 10.1007/s00129-020-04637-9. View

Remmele W, Schicketanz K . Immunohistochemical determination of estrogen and progesterone receptor content in human breast cancer. Computer-assisted image analysis (QIC score) vs. subjective grading (IRS). Pathol Res Pract. 1993; 189(8):862-6. DOI: 10.1016/S0344-0338(11)81095-2. View

Naeh A, Berezowsky A, Yudin M, Dhalla I, Berger H . Preeclampsia-Like Syndrome in a Pregnant Patient With Coronavirus Disease 2019 (COVID-19). J Obstet Gynaecol Can. 2021; 44(2):193-195. PMC: 8505022. DOI: 10.1016/j.jogc.2021.09.015. View

Argueta L, Lacko L, Bram Y, Tada T, Carrau L, Rendeiro A . Inflammatory responses in the placenta upon SARS-CoV-2 infection late in pregnancy. iScience. 2022; 25(5):104223. PMC: 8996470. DOI: 10.1016/j.isci.2022.104223. View

10.

Remmele W, Stegner H . [Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue]. Pathologe. 1987; 8(3):138-40. View

11.

Gabby L, Jones C, McIntyre B, Manalo Z, Meads M, Pizzo D . Chronic villitis as a distinctive feature of placental injury in maternal SARS-CoV-2 infection. Am J Obstet Gynecol. 2024; 232(1):123.e1-123.e12. DOI: 10.1016/j.ajog.2024.04.002. View

12.

Bordt E, Shook L, Atyeo C, Pullen K, De Guzman R, Meinsohn M . Maternal SARS-CoV-2 infection elicits sexually dimorphic placental immune responses. Sci Transl Med. 2021; 13(617):eabi7428. PMC: 8784281. DOI: 10.1126/scitranslmed.abi7428. View

13.

Accurti V, Gambitta B, Iodice S, Manenti A, Boito S, Dapporto F . SARS-CoV-2 Seroconversion and Pregnancy Outcomes in a Population of Pregnant Women Recruited in Milan, Italy, between April 2020 and October 2020. Int J Environ Res Public Health. 2022; 19(24). PMC: 9778651. DOI: 10.3390/ijerph192416720. View

14.

Hagenbeck C, Zollkau J, Helbig M, Fehm T, Schaal N . COVID-19 Vaccination during Pregnancy and Lactation: Attitudes and Uptakes before and after Official Recommendations in Germany. Vaccines (Basel). 2023; 11(3). PMC: 10056568. DOI: 10.3390/vaccines11030627. View

15.

Enninga E, Quach H, Jang J, de Araujo Correia M, Fedyshyn Y, Fedyshyn B . Maternal SARS-CoV-2 infection in pregnancy disrupts gene expression in Hofbauer cells with limited impact on cytotrophoblasts. PLoS Pathog. 2024; 20(2):e1011990. PMC: 10878512. DOI: 10.1371/journal.ppat.1011990. View

16.

Mittelberger J, Seefried M, Franitza M, Garrido F, Ditsch N, Jeschke U . The Role of the Immune Checkpoint Molecules PD-1/PD-L1 and TIM-3/Gal-9 in the Pathogenesis of Preeclampsia-A Narrative Review. Medicina (Kaunas). 2022; 58(2). PMC: 8880413. DOI: 10.3390/medicina58020157. View

17.

Acheampong K, Schaff D, Emert B, Lake J, Reffsin S, Shea E . Subcellular Detection of SARS-CoV-2 RNA in Human Tissue Reveals Distinct Localization in Alveolar Type 2 Pneumocytes and Alveolar Macrophages. mBio. 2022; 13(1):e0375121. PMC: 8822351. DOI: 10.1128/mbio.03751-21. View

18.

Meister S, Dreyer E, Hahn L, Thomann M, Keilmann L, Beyer S . Risk of postpartum depressive symptoms is influenced by psychological burden related to the COVID-19 pandemic and dependent of individual stress coping. Arch Gynecol Obstet. 2022; 308(6):1737-1748. PMC: 9735014. DOI: 10.1007/s00404-022-06854-0. View

19.

Celewicz A, Celewicz M, Michalczyk M, Wozniakowska-Gondek P, Krejczy K, Misiek M . SARS CoV-2 infection as a risk factor of preeclampsia and pre-term birth. An interplay between viral infection, pregnancy-specific immune shift and endothelial dysfunction may lead to negative pregnancy outcomes. Ann Med. 2023; 55(1):2197289. PMC: 10120558. DOI: 10.1080/07853890.2023.2197289. View

20.

Tosto V, Meyyazhagan A, Alqasem M, Tsibizova V, Di Renzo G . SARS-CoV-2 Footprints in the Placenta: What We Know after Three Years of the Pandemic. J Pers Med. 2023; 13(4). PMC: 10142804. DOI: 10.3390/jpm13040699. View