The bitter side of sweet: the role of Galectin‐9 in immunopathogenesis of viral infections

Summary In recent years, a critical role for β‐galactoside‐binding protein, Galectin‐9 (Gal‐9) has emerged in infectious disease, autoimmunity, and cancer. It is a ligand for T cell immunoglobulin mucin domain 3 (Tim‐3), a type‐I glycoprotein that is persistently expressed on dysfunctional T cells during chronic viral infections. Gal‐9 exerts its pivotal immunomodulatory effects by inducing apoptosis or suppressing effector functions via engagement with its receptor, Tim‐3. Recent studies report elevation of circulating Gal‐9 in humans infected with different viral infections. Interaction of soluble Gal‐9 with Tim‐3 expressed on the surface of activated CD4+ T cells renders them less susceptible to HIV‐1 infection, while enhanced HIV infection occurs when Gal‐9 interacts with a different receptor than Tim‐3. This indicates the versatile role of Gal‐9 in viral pathogenesis. For instance, higher expression of Tim‐3 during chronic viral infection and elevation of plasma Gal‐9 may have evolved to limit persistent immune activation and pathogenic T cells activity. In contrast, Gal‐9 can suppress the effectiveness of immunity against viral infections. In agreement, Gal‐9 knockout mice mount a more robust and vigorous virus‐specific immune response in acute and chronic viral infections resulting in rapid viral clearance. In line with this observation, blocking Gal‐9 signals to Tim‐3‐expressing T cells result in improved immune responses...
Source: Reviews in Medical Virology - Category: Virology Authors: Tags: Review Source Type: research