Influenza and Bacterial Superinfection: Illuminating the Immunologic Mechanisms of Disease

Abstract

Seasonal influenza virus infection presents a major strain on the health care system. Influenza virus infection has pandemic potential, which was repeatedly observed during the last century. Severe disease may occur in the young, in the elderly, in those with preexisting lung disease, and in previously healthy individuals. A common cause of severe influenza pathogenesis is superinfection with bacterial pathogens, namely, Staphylococcus aureus and Streptococcus pneumoniae. A great deal of recent research has focused on the immune pathways involved in influenza-induced susceptibility to secondary bacterial pneumonia. Both innate and adaptive antibacterial host defenses are impaired in the context of preceding influenza virus infection. The goal of this minireview is to highlight these findings and synthesize these data into a shared central theme of pathogenesis.

FIG 1

Common pathways of susceptibility to postinfluenza bacterial superinfections. Early after influenza virus infection, mice show reduced susceptibility to superinfection that is at least in part due to increased production of IL-13. This IL-13-rich environment does not permit IFN-γ production, allowing unaltered phagocytosis and clearance of bacteria. The role for either neutrophils or macrophages (phagocytes) in bacterial clearance early during influenza virus infection has not been fully investigated. Progression of influenza virus infection results in increased susceptibility to secondary infection. Type I IFN (or IL-27) signaling initiated in response to influenza virus infection results in downregulated production of IL-1β and Il-23 and impaired type 17 immune responses. Inhibition of IL-17 and IL-22 reduces production of antimicrobial peptides. Type I IFN signaling also reduces levels of neutrophil chemoattractants Cxcl1 and Cxcl2 and can induce formation of NETs. IL-27 induced during influenza virus infection further suppresses IL-17 production but stimulates production of regulatory cytokine IL-10, which contributes to increased susceptibility to superinfection, presumably by alteration of the anti-influenza inflammatory response. IAV, influenza A virus infection.