title: T cell immunoglobulin and mucin protein-3 (Tim-3)/Galectin-9 interaction regulates influenza A virus-specific humoral and CD8 T-cell responses.
abstract: Reactions to pathogens are usually tuned to effect immunity and limit tissue damage. Several host counterinflammatory mechanisms inhibit tissue damage but these may also act to constrain the effectiveness of immunity to acute infections, as we demonstrate in mice acutely infected with influenza A virus (IAV). We show that compared with wild type (WT), galectin-9 knockout (G9KO) mice mounted a more robust acute phase virus-specific CD8 T-cell response as well as higher and more rapid virus-specific serum IgM, IgG, and IgA responses and also cleared virus more rapidly than did WT mice. Blocking galectin-9 signals to Tim-3-expressing cells using a Tim-3 fusion protein resulted in improved immune responses in WT mice. When IAV immune mice were challenged with a heterologous IAV, the secondary IAV-specific CD8 T-cell responses were four- to fivefold higher in G9KO compared with WT mice. Our results indicate that manipulating galectin signals may represent a convenient approach to improve immune responses to some vaccines.
authors: Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996-0845, USA.
authors: Shalini
authors: S
authors: Sharma
authors: Aarthi
authors: A
authors: Sundararajan
authors: Amol
authors: A
authors: Suryawanshi
authors: Naveen
authors: N
authors: Kumar
authors: Tamara
authors: T
authors: Veiga-Parga
authors: Vijay K
authors: VK
authors: Kuchroo
authors: Paul G
authors: PG
authors: Thomas
authors: Mark Y
authors: MY
authors: Sangster
authors: Barry T
authors: BT
authors: Rouse
mesh_terms: D000210:Acute-Phase Reaction / Q000276:immunology; D000704:Analysis of Variance; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D037161:Galectins / Q000235:genetics / Q000276:immunology*; D000072597:Hepatitis A Virus Cellular Receptor 2; D056724:Immunity, Humoral / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D011991:Receptors, Virus / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D037161:Galectins; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D011991:Receptors, Virus; C508186:galectin 9, mouse