title: The bitter side of sweet: the role of Galectin-9 in immunopathogenesis of viral infections.
abstract: 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. Here we review the biological and immunological properties of Gal-9 in viral infections (HIV, HCV, HBV, HSV, CMV, influenza, and dengue virus). Manipulating Gal-9 signals may have immunotherapeutic potential and could represent an alternative approach for improving immune responses to viral infections/vaccines.
authors.affiliation: Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada; Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
authors.forename: Shahzma
authors.initials: S
authors.lastname: Merani
authors.forename: Wenna
authors.initials: W
authors.lastname: Chen
authors.forename: Shokrollah
authors.initials: S
authors.lastname: Elahi
mesh_terms: D000818:Animals; D037161:Galectins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D056747:Immunomodulation; D014777:Virus Diseases / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000821:virology
chemical_list: D037161:Galectins; C105032:LGALS9 protein, human