Increased Levels of Plasma Galectin-9 in Patients with Influenza Virus Infection

Abstract

Galectin-9 (Gal-9) is a β-galactoside-binding protein involved in various biologic processes, including cell aggregation, adhesion, chemoattraction, and apoptosis. Little is known, however, about the regulation mechanisms of Gal-9 production. Recent studies reported high plasma Gal-9 levels in humans infected with human immunodeficiency virus-1 and dengue virus. Viral respiratory infections such as influenza are common human illnesses. A synthetic double-stranded RNA, polyinosinic-polycytidylic acid (PolyIC), mimics the effects of viruses in various cell types and induces the expression of Gal-9 in endothelial cells. To examine the potential link between viral infection and Gal-9 expression, we measured plasma Gal-9 concentrations in patients with influenza. Subjects were 43 patients with influenza virus infection, 20 with pneumococcal pneumonia, and 20 healthy adults. Gal-9 concentrations in the plasma and in culture supernatants of human airway epithelial cells were measured using an enzyme-linked immunosorbent assay. Plasma Gal-9 concentrations were higher in patients with influenza infection than in patients with pneumococcal pneumonia and healthy subjects (p < 0.05). Patients with influenza were effectively differentiated from those with pneumococcal pneumonia or healthy subjects, based on the plasma levels of Gal-9 (p < 0.0001). Furthermore, using a human airway epithelial cell line, we showed that the presence of PolyIC but not lipopolysaccharides increased the Gal-9 concentration in the culture medium (p < 0.05), suggesting that PolyIC enhanced Gal-9 production. These findings support our proposal that Gal-9 production is induced by influenza virus infection in humans. In conclusion, plasma Gal-9 could be a new biomarker for patients with influenza infection.

Galectin-1, -3 and -9 Expression and Clinical Significance in Squamous Cervical Cancer

“…In cervical cancer, a correlation with high differentiation grade has been described for galectin-9 expression [31], in agreement with the trend toward improved prognosis described in our study. Tumor galectin-9 expression might be related to HPV infection, as different viruses including human cytomegalovirus, HIV and influenza virus have been shown to induce galectin-9 expression [43–45]. We found that galectin-3 and galectin-9 expression were both significantly correlated with HPV16 or HPV18 expression, supporting this hypothesis.…”

Human Cytomegalovirus Upregulates Expression of the Lectin Galectin 9 via Induction of Beta Interferon

“…Indeed, individuals infected with hepatitis C virus (HCV), HIV-1, dengue virus, and influenza virus have higher serum levels of Gal-9 (6,(22)(23)(24), yet the mechanism responsible for such increases has not been identified. Given the critical role of type I IFNs in controlling viral infections, it is tempting to speculate that IFN-␤ may be an essential driver of Gal-9 upregulation.…”

Increased Galectin-9 Concentration and Number of CD4+Foxp3high+Cells in Bronchoalveolar Lavage Fluid of Patients with Cryptogenic Organizing Pneumonia

“…There were no current smokers at the time of the study. Smoking status had no influence on the Gal-9 levels in the BALF in a previous study [17]. Surfactant protein D and lactate dehydrogenase were similar, but Krebs von den Lungen-6 was significantly lower in patients with COP than in patients with IPF (p \ 0.05).…”

“…Mouse monoclonal antibody against human Gal-9 (9S2-3) and polyclonal rabbit anti-human Gal-9 antibody were purchased from GalPharma (Takamatsu, Japan) [17]. Human lung fibroblast cells, fibroblast basal medium, and supplements for fibroblast culture were purchased from Lonza (Walkersville, MD, USA).…”

“…Gal-9 levels in the BALF were measured by ELISA using the 9S2-3 antibody, as previously described [17]. TGF-b1 and IL-10 levels in the BALF were measured using the respective ELISA kits (BioSource International, Camarillo, CA, USA, and R&D Systems, Minneapolis, MN, USA, respectively).…”