Compromised Defenses: Exploitation of Epithelial Responses During Viral-Bacterial Co-Infection of the Respiratory Tract

Respiratory infections are the greatest single contributor to the overall burden of disease worldwide [1]. Polymicrobial infections are becoming increasingly recognized in terms of both prevalence and their effect on disease severity, causing many common diseases such as oral infections, otitis media, chronic wound infections, and implanted medical device infections, as well as chronic pulmonary disease in cystic fibrosis patients [2,3]. There is a large body of literature demonstrating synergy between viral and bacterial infections at mucosal surfaces; for example, (i) the intestinal microbiota promotes enteric viral infection via direct interactions and modulation of the immune system [4]; (ii) sexually transmitted viruses exploit the altered environment, including altered pH, inflammatory, and oxidative settings, during bacterial vaginosis or aerobic vaginitis to increase infection of the vaginal and cervical epithelium [5]; and (iii) bacteria take advantage of the altered innate and adaptive immune responses of the respiratory tract during viral infection of the respiratory epithelium to increase infectivity and virulence [6]. Many studies have focused on the consequences of influenza infection on secondary bacterial infection in the respiratory tract, where altered lung physiology and immune status increases susceptibility to severe secondary bacterial infections with common commensal organisms of the upper respiratory tract, such as Streptococcus pneumoniae and Staphylococcus aureus [7]. Here, we focus on the role of the respiratory epithelium in defending against microbial pathogens as well as in facilitating synergistic pathogenic interactions (Fig 1).