The role of interferon lambda during influenza, Staphylococcus aureus super-infection.

Abstract

Abstract While pandemic influenza A H1N1 infection causes significant morbidity and mortality on its own, it also renders an individual more susceptible to secondary infection with bacterial pathogens such as Staphylococcus aureus. We have previously shown that type I interferons produced by influenza impair bacterial defense six to seven days post-influenza infection. However, the role of the predominant type III interferons (interferon lambda/IFNL, IL-28A/B) in bacterial super-infection is less clear. Thus, we explored the role of IFNL in influenza, S. aureus super-infection. First, we examined the impact of attenuating IFNL signaling directly before bacterial challenge. We found that treatment with the IFNLR1 Fc protein significantly increased bacterial burden in the lung compared with controls. However, when we challenged mice with super-infection that have constitutively attenuated IFNL, we found reduced bacterial burden compared to controls, which was significantly correlated with the degree of IFNL expression. While cellular inflammation was not altered, preliminary results suggest that higher bacterial burden is significantly correlated with higher weight loss, suggesting that mice with constitutively attenuated IFNL are protected from both influenza infection and bacterial super-infection. It has been published that mice lacking IFNL receptor 1 have lower bacterial burden during super-infection, which is corroborated by data from our constitutively attenuated IFNL mice. However, attenuation of IFNL signaling directly prior to bacterial challenge increases bacterial burden, suggesting that the timing of IFNL production regulates susceptibility to secondary bacterial infection.