title: Desialylation of airway epithelial cells during influenza virus infection enhances pneumococcal adhesion via galectin binding.
abstract: The continued threat of worldwide influenza pandemics, together with the yearly emergence of antigenically drifted influenza A virus (IAV) strains, underscore the urgent need to elucidate not only the mechanisms of influenza virulence, but also those mechanisms that predispose influenza patients to increased susceptibility to subsequent infection with Streptococcus pneumoniae. Glycans displayed on the surface of epithelia that are exposed to the external environment play important roles in microbial recognition, adhesion, and invasion. It is well established that the IAV hemagglutinin and pneumococcal adhesins enable their attachment to the host epithelia. Reciprocally, the recognition of microbial glycans by host carbohydrate-binding proteins (lectins) can initiate innate immune responses, but their relevance in influenza or pneumococcal infections is poorly understood. Galectins are evolutionarily conserved lectins characterized by affinity for β-galactosides and a unique sequence motif, with critical regulatory roles in development and immune homeostasis. In this study, we examined the possibility that galectins expressed in the airway epithelial cells might play a significant role in viral or pneumococcal adhesion to airway epithelial cells. Our results in a mouse model for influenza and pneumococcal infection revealed that the murine lung expresses a diverse galectin repertoire, from which selected galectins, including galectin 1 (Gal1) and galectin 3 (Gal3), are released to the bronchoalveolar space. Further, the results showed that influenza and subsequent S. pneumoniae infections significantly alter the glycosylation patterns of the airway epithelial surface and modulate galectin expression. In vitro studies on the human airway epithelial cell line A549 were consistent with the observations made in the mouse model, and further revealed that both Gal1 and Gal3 bind strongly to IAV and S. pneumoniae, and that exposure of the cells to viral neuraminidase or influenza infection increased galectin-mediated S. pneumoniae adhesion to the cell surface. Our results suggest that upon influenza infection, pneumococcal adhesion to the airway epithelial surface is enhanced by an interplay among the host galectins and viral and pneumococcal neuraminidases. The observed enhancement of pneumococcal adhesion may be a contributing factor to the observed hypersusceptibility to pneumonia of influenza patients.
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA; Institute of Marine and Environmental Technology, Columbus Center, 701 East Pratt Street, Baltimore, MD 21202, USA.
authors.forename: Mihai
authors.initials: M
authors.lastname: Nita-Lazar
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA; Institute of Marine and Environmental Technology, Columbus Center, 701 East Pratt Street, Baltimore, MD 21202, USA.
authors.forename: Aditi
authors.initials: A
authors.lastname: Banerjee
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA; Institute of Marine and Environmental Technology, Columbus Center, 701 East Pratt Street, Baltimore, MD 21202, USA.
authors.forename: Chiguang
authors.initials: C
authors.lastname: Feng
authors.affiliation: Institute of Human Virology and Department of Biochemistry & Molecular Biology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA.
authors.forename: Mohammed N
authors.initials: MN
authors.lastname: Amin
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Frieman
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: Wilbur H
authors.initials: WH
authors.lastname: Chen
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Cross
authors.affiliation: Institute of Human Virology and Department of Biochemistry & Molecular Biology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA.
authors.forename: Lai-Xi
authors.initials: LX
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA; Institute of Marine and Environmental Technology, Columbus Center, 701 East Pratt Street, Baltimore, MD 21202, USA. Electronic address: GVasta@som.umaryland.edu.
authors.forename: Gerardo R
authors.initials: GR
authors.lastname: Vasta
mesh_terms: D018829:Adhesins, Bacterial; D000818:Animals; D017209:Apoptosis; D001422:Bacterial Adhesion / Q000502:physiology; D002460:Cell Line; D004198:Disease Susceptibility; D004847:Epithelial Cells / Q000378:metabolism; D037483:Galectin 1 / Q000096:biosynthesis / Q000378:metabolism*; D037502:Galectin 3 / Q000096:biosynthesis / Q000378:metabolism*; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity; D051379:Mice; D008810:Mice, Inbred C57BL; D009439:Neuraminidase / Q000494:pharmacology; D009976:Orthomyxoviridae Infections / Q000473:pathology*; D011008:Pneumococcal Infections / Q000473:pathology*; D011485:Protein Binding / Q000187:drug effects; D020545:Respiratory Mucosa / Q000166:cytology* / Q000382:microbiology / Q000821:virology; D013296:Streptococcus pneumoniae / Q000472:pathogenicity
chemical_list: D018829:Adhesins, Bacterial; D037483:Galectin 1; D037502:Galectin 3; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D009439:Neuraminidase
keywords: Airway A549 cells; Galectin; Influenza; Neuraminidase; Pneumococcus pneumoniae