Title | Human galectin-9 potently enhances SARS-CoV-2 replication and inflammation in airway epithelial cells. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Du, L, Bouzidi, MS, Gala, A, Deiter, F, Billaud, J-N, Yeung, ST, Dabral, P, Jin, J, Simmons, G, Dossani, ZY, Niki, T, Ndhlovu, LC, Greenland, JR, Pillai, SK |
Journal | J Mol Cell Biol |
Volume | 15 |
Issue | 4 |
Date Published | 2023 Aug 03 |
ISSN | 1759-4685 |
Keywords | Angiotensin-Converting Enzyme 2, COVID-19, Epithelial Cells, Galectins, Humans, Inflammation, SARS-CoV-2 |
Abstract | The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a global economic and health crisis. Recently, plasma levels of galectin-9 (Gal-9), a β-galactoside-binding lectin involved in immune regulation and viral immunopathogenesis, were reported to be elevated in the setting of severe COVID-19 disease. However, the impact of Gal-9 on SARS-CoV-2 infection and immunopathology remained to be elucidated. In this study, we demonstrate that Gal-9 treatment potently enhances SARS-CoV-2 replication in human airway epithelial cells (AECs), including immortalized AECs and primary AECs cultured at the air-liquid interface. Gal-9-glycan interactions promote SARS-CoV-2 attachment and entry into AECs in an angiotensin-converting enzyme 2 (ACE2)-dependent manner, enhancing the binding of the viral spike protein to ACE2. Transcriptomic analysis revealed that Gal-9 and SARS-CoV-2 infection synergistically induced the expression of key pro-inflammatory programs in AECs, including the IL-6, IL-8, IL-17, EIF2, and TNFα signaling pathways. Our findings suggest that manipulation of Gal-9 should be explored as a therapeutic strategy for SARS-CoV-2 infection. |
DOI | 10.1093/jmcb/mjad030 |
Alternate Journal | J Mol Cell Biol |
PubMed ID | 37127426 |
PubMed Central ID | PMC10668544 |
Grant List | I01 CX002011 / CX / CSRD VA / United States P30 AI027763 / AI / NIAID NIH HHS / United States R01 MH112457 / MH / NIMH NIH HHS / United States R01MH112457 / NH / NIH HHS / United States |