The role of interleukin-27 in influenza A and Staphylococcus aureus co-infection (INC8P.435)

Rationale: Influenza A represents a significant cause of worldwide morbidity and mortality and results in increased susceptibility to secondary bacterial infections in the lung. We have previously shown that Influenza A impairs bacterial host defense through inhibition of Type 17 immunity. IL-27 is known to inhibit Type 17 immunity, suggesting a potential critical role for IL-27 in viral and bacterial co-infection. Methods: Wild-type and IL-27 receptor α knock-out (IL-27Ra-/-) mice were infected with Influenza A H1N1 (PR/8/34) or vehicle for 6 days followed by challenge with Staphylococcus aureus (ATCC 49775) or vehicle for 24 hours. Lung inflammation, bacterial burden, gene expression, and cytokine production were determined. Results: IL-27Ra-/- mice challenged with influenza A had increased weight loss compared to controls. In addition, IL-27Ra-/- mice displayed significantly decreased IL-10 production. IL-27Ra-/- mice co-infected with influenza and S. aureus had improved bacterial clearance compared to wild-type controls despite worsened lung pathology. Importantly, there were increased IL-17 and IL-22 expression and significantly decreased IL-10 production in the IL-27Ra-/- mice. Conclusions: These data suggest that IL-27 contributes to enhanced susceptibility to S. aureus pneumonia following influenza infection through the induction of IL-10 and regulation of Type 17 immunity.