Timing of post-influenza bacterial superinfection with MRSA dictates the outcome of MRSA pneumonia in mice (P4027)

Abstract

Abstract Secondary bacterial pneumonias caused by S. aureus, S. pneumoniae and H. influenzae are a common occurrence following influenza infection and are responsible for significant morbidity and mortality worldwide. Others have shown in murine models that 5-8 days after influenza challenge the susceptibility to secondary bacterial infections increases; though the mechanism of this increased susceptibility is still elusive. Here, we report that 2-3 days after influenza challenge (before the onset of clinical symptoms, i.e. body weight loss) mice actually have increased resistance to secondary infection with methicillin resistant S. aureus (MRSA). Importantly, despite this early protection from MRSA, the response to bacteria early in the influenza infection results in increased viral growth and subsequently death of mice. The mechanism of this increased resistance to secondary MRSA pneumonia early after influenza is dependent on the transient presence of IL-13 and on type I IFN signaling, as mice deficient in these cytokine or cytokine receptor do not show increased resistance to secondary MRSA pneumonia 2-3 days after influenza infection, and injection of exogenous IL-13 to mice co-infected with MRSA pneumonia on day 7 increases resistance to bacteria. Thus, depending on the time of secondary infection in relation to influenza, the disease phenotype contracted by mice is greatly different, awareness of which is important for the design of rational treatments in clinics.