FIG 1 .

Roles of endogenous danger signals during influenza A viral infection. Endogenous danger signals, including ATP, glucose, norepinephrine, and febrile temperature ranges, are elicited from damaged cells following influenza A virus (IAV) infection. These danger signals influence the infective potential of commensal Staphylococcus aureus, as well as potentially manipulating innate immune responses. (A) A combination of danger signals initiates dispersal of S. aureus biofilms in the nasal cavity, leading to dissemination of the bacteria from the nasal epithelium to the lungs. (B) ATP can trigger the innate immune response against IAV by activating the NLRP3 inflammasome in macrophages, leading to secretion of IL-1β and the initiation of a proinflammatory response. (C) High levels of glucose can negatively affect collectin-mediated immune defenses in the lung against IAV. (i) Collectin surfactant protein D (SP-D) can neutralize the infectivity of IAV by binding to oligosaccharides on viral glycoproteins. (ii) Glucose is a ligand for SP-D. Binding of glucose to SP-D acts to inhibit SP-D-mediated antiviral activity.