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.