A unique maternal and placental galectin signature upon SARS-CoV-2 infection suggests galectin-1 as a key alarmin at the maternal–fetal interface

• Published in: Frontiers in immunology Vol. 14; p. 1196395
• Main Authors: Zhao, Fangqi, Tallarek, Ann-Christin, Wang, Yiru, Xie, Yiran, Diemert, Anke, Lu-Culligan, Alice, Vijayakumar, Pavithra, Kittmann, Enrico, Urbschat, Christopher, Bayo, Juan, Arck, Petra C., Farhadian, Shelli F., Dveksler, Gabriela S., Garcia, Mariana G., Blois, Sandra M.
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 05.07.2023
• Subjects: Alarmins - metabolism; COVID-19 - metabolism; Female; Galectin 1 - metabolism; galectin-1; galectin-3; galectin-7; galectin-9; Galectins - metabolism; Humans; Immunology; Infant, Newborn; Placenta; Pregnancy; PSG1; SARS-CoV-2; SARS-CoV-2 - metabolism; COVID-19; galectin-7; SARS-CoV-2; galectin-9; PSG1; galectin-3; galectin-1
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1196395

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic imposed a risk of infection and disease in pregnant women and neonates. Successful pregnancy requires a fine-tuned regulation of the maternal immune system to accommodate the growing fetus and to protect the mother from infection. Galectins, a family of β-galactoside–binding proteins, modulate immune and inflammatory processes and have been recognized as critical factors in reproductive orchestration, including maternal immune adaptation in pregnancy. Pregnancy-specific glycoprotein 1 (PSG1) is a recently identified gal-1 ligand at the maternal–fetal interface, which may facilitate a successful pregnancy. Several studies suggest that galectins are involved in the immune response in SARS-CoV-2–infected patients. However, the galectins and PSG1 signature upon SARS-CoV-2 infection and vaccination during pregnancy remain unclear. In the present study, we examined the maternal circulating levels of galectins (gal-1, gal-3, gal-7, and gal-9) and PSG1 in pregnant women infected with SARS-CoV-2 before vaccination or uninfected women who were vaccinated against SARS-CoV-2 and correlated their expression with different pregnancy parameters. SARS-CoV-2 infection or vaccination during pregnancy provoked an increase in maternal gal-1 circulating levels. On the other hand, levels of PSG1 were only augmented upon SARS-CoV-2 infection. A healthy pregnancy is associated with a positive correlation between gal-1 concentrations and gal-3 or gal-9; however, no correlation was observed between these lectins during SARS-CoV-2 infection. Transcriptome analysis of the placenta showed that gal-1, gal-3, and several PSG and glycoenzymes responsible for the synthesis of gal-1-binding glycotopes (such as linkage-specific N-acetyl-glucosaminyltransferases (MGATs)) are upregulated in pregnant women infected with SARS-CoV-2. Collectively, our findings identify a dynamically regulated “galectin-specific signature” that accompanies the SARS-CoV-2 infection and vaccination in pregnancy, and they highlight a potentially significant role for gal-1 as a key pregnancy protective alarmin during virus infection.