Dataset Information

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.

SUBMITTER: Sharma S

PROVIDER: S-EPMC3223445 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

T cell immunoglobulin and mucin protein-3 (Tim-3)/Galectin-9 interaction regulates influenza A virus-specific humoral and CD8 T-cell responses.

Sharma Shalini S Sundararajan Aarthi A Suryawanshi Amol A Kumar Naveen N Veiga-Parga Tamara T Kuchroo Vijay K VK Thomas Paul G PG Sangster Mark Y MY Rouse Barry T BT

Proceedings of the National Academy of Sciences of the United States of America 20111103 47

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-specif ...[more]

PMID: 22052881

Similar Datasets

Project description:Hepatic ischemia-reperfusion injury (IRI), an innate immunity-driven inflammation response, occurs in multiple clinical settings including liver resection, transplantation, trauma, and shock. T-cell immunoglobulin and mucin (TIM)-4, the only TIM protein not expressed on T cells, is found on macrophages and dendritic cells. The regulatory function of macrophage TIM-4 in the engulfment of apoptotic/necrotic bodies in innate immunity-mediated disease states remains unknown. This study focuses on the putative role of TIM-4 signaling in a model of liver warm ischemia (90 minutes) and reperfusion. The ischemia insult triggered TIM-4 expression by stressed hepatocellular phosphatidylserine (PS) presentation, peaking at 6 hours of reperfusion, and coinciding with the maximal hepatocellular damage. TIM-4-deficient or wild-type WT mice treated with antagonistic TIM-4 monoclonal antibody (mAb) were resistant against liver IRI, evidenced by diminished serum alanine aminotransferase (sALT) levels and well-preserved hepatic architecture. Liver hepatoprotection rendered by TIM-4 deficiency was accompanied by diminished macrophage infiltration/chemoattraction, phagocytosis, and activation of Toll-like receptor (TLR)2/4/9-dependent signaling. Correlating with in vivo kinetics, the peak of TIM-4 induction in lipopolysaccharide (LPS)-activated bone marrow derived-macrophages (BMM) was detected in 6-hour cultures. To mimic liver IRI, we employed hydrogen peroxide-necrotic hepatocytes, which readily present PS. Indeed, necrotic hepatocytes were efficiently captured/engulfed by WT (TIM-4+) but not by TIM-4-deficient BMM. Finally, in a newly established model of liver IRI, adoptive transfer of WT but not TIM-4-deficient BMM readily recreated local inflammation response/hepatocellular damage in the CD11b-DTR mouse system.These findings document the importance of macrophage-specific TIM-4 activation in the mechanism of hepatic IRI. Macrophage TIM-4 may represent a therapeutic target to minimize innate inflammatory responses in IR-stressed organs.

Dataset Information

T cell immunoglobulin and mucin protein-3 (Tim-3)/Galectin-9 interaction regulates influenza A virus-specific humoral and CD8 T-cell responses.

Publications

T cell immunoglobulin and mucin protein-3 (Tim-3)/Galectin-9 interaction regulates influenza A virus-specific humoral and CD8 T-cell responses.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets