Galectins regulate the inflammatory response in airway epithelial cells exposed to microbial neuraminidase by modulating the expression of SOCS1 and RIG1

Mol Immunol. 2015 Dec;68(2 Pt A):194-202. doi: 10.1016/j.molimm.2015.08.005. Epub 2015 Sep 6.


Influenza patients frequently display increased susceptibility to Streptococcus pneumoniae co-infection and sepsis, the prevalent cause of mortality during influenza pandemics. However, the detailed mechanisms by which an influenza infection predisposes patients to suffer pneumococcal pneumonia are not fully understood. A murine model for influenza infection closely reflects the observations in human patients, since if the animals that have recovered from influenza A virus (IAV) sublethal infection are challenged with S. pneumoniae, they undergo a usually fatal uncontrolled cytokine response. We have previously demonstrated both in vitro and in vivo that the expression and secretion of galectin-1 (Gal1) and galectin-3 (Gal3) are modulated during IAV infection, and that the viral neuraminidase unmasks galactosyl moieties in the airway epithelia. In this study we demonstrate in vitro that the binding of secreted Gal1 and Gal3 to the epithelial cell surface modulates the expression of SOCS1 and RIG1, and activation of ERK, AKT or JAK/STAT1 signaling pathways, leading to a disregulated expression and release of pro-inflammatory cytokines. Our results suggest that the activity of the viral and pneumococcal neuraminidases on the surface of the airway epithelial cells function as a "danger signal" that leads to rapid upregulation of SOCS1 expression to prevent an uncontrolled inflammatory response. The binding of extracellular Gal1 or Gal3 to the galactosyl moieties unmasked on the surface of airway epithelial cells can either "fine-tune" or severely disregulate this process, respectively, the latter potentially leading to hypercytokinemia.

Keywords: Chemokines; Cytokines; Galectin; Neuraminidase; RIG1; SOCS; Signaling pathway.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacterial Proteins / pharmacology
  • Cell Line, Tumor
  • Cytokines / biosynthesis
  • Cytokines / metabolism
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / genetics*
  • DEAD-box RNA Helicases / immunology
  • DEAD-box RNA Helicases / pharmacology
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / immunology
  • Galectin 1 / biosynthesis
  • Galectin 1 / immunology
  • Galectin 1 / pharmacology*
  • Galectin 3 / biosynthesis
  • Galectin 3 / immunology
  • Galectin 3 / pharmacology*
  • Gene Expression Regulation
  • Humans
  • Inflammation
  • Influenza A virus / immunology
  • Janus Kinases / genetics
  • Janus Kinases / immunology
  • Mice
  • Neuraminidase / pharmacology
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / immunology
  • Receptors, Immunologic
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / immunology
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / immunology
  • Signal Transduction
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics*
  • Suppressor of Cytokine Signaling Proteins / immunology
  • Suppressor of Cytokine Signaling Proteins / pharmacology


  • Bacterial Proteins
  • Cytokines
  • Galectin 1
  • Galectin 3
  • LGALS1 protein, human
  • Receptors, Immunologic
  • Recombinant Proteins
  • SOCS1 protein, human
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Janus Kinases
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • Neuraminidase
  • DDX58 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases