Fig 4.

Mechanisms by which HRV increases susceptibility to bacterial infection. (1) HRVs disrupt epithelial cell barrier function by the dissociation of zona occludens 1 (ZO-1) from the tight junction complex via the increased generation of reactive oxygen species (ROS), thereby facilitating the transmigration of bacteria (28). (2) HRVs promote Staphylococcus aureus internalization into non-fully permissive cultured pneumocytes via the increased release of IL-6 and IL-8 and expression of intercellular adhesion molecule 1 (ICAM-1) on neighboring uninfected cells (175). (3) HRVs stimulate Streptococcus pneumoniae adhesion to human tracheal epithelial cells by inducing the surface expression of platelet-activating factor receptor (PAFR) via NF-κβ expression (173) and to nasal epithelial cells via increased gene and protein expression levels of fibronectin, PAFR, and carcinoembryonic antigen-related cell adhesion molecule (174). (4) Compared to non-HRV-activated macrophages, HRV-activated macrophages demonstrate reduced levels of secretion of TNF-α and IL-8 when exposed to bacterial Toll-like receptors (TLRs) (lipopolysaccharide and lipoteichoic acid) (176). SP-1, promoter-specific transcription factor 1.