FIGURE 1.

Potential implication of galectin-3 in the pathogenesis of severe COVID-19 cases. Infection of type II alveolar cells by SARS-CoV-2 is driven by ACE2-spike protein interaction and supported by CD147 and CD26 interaction. Gal3 can mediate ligand-receptor interaction by glycan recognition of spike protein and interaction with receptors. In particular, CD147-spike protein interaction promotes apoptosis of T-lymphocytes provoking systemic lymphocytopenia syndrome. Lysis of infected cells provoke the secretion of DAMPs and PAMPs recognized by alveolar macrophages receptors like triggering receptor expressed on myeloid cells 2 (TREM2) or toll-like receptors (TLRs) that trigger the upregulation of several cytokines including IL-6, TNFα and gal3. TLRs activation induces the assembly of the macromolecular platform known as inflammasome that promotes the cleavage of pro-IL-1β into active IL-1β and the cleavage of gasdermin-D (GSDMD), thus promoting pores formation in the cell membrane and induce the secretion of IL-1β. This macrophage activation triggers the hyperinflammation phase called “cytokine storm” and is supported by lymphocyte infiltration and proliferation with high expression of gal3 that contributes to the cytokine storm. The macrophage activation is composed of several phenotypes. A subset of macrophages develop a pro-fibrotic phenotype controlled by TREM2 and gal3 expression that triggers lung fibrosis. Moreover, hypoxia triggers gal3 expression by endothelial and smooth muscle cells. Lastly, comorbidities like diabetes, pneumonia or cardiovascular diseases increase basal levels of plasma gal3 what would contribute to COVID-19 severe prognosis.