The majority of deaths following influenza virus
infection result from secondary bacterial
superinfection, most commonly caused by Streptococcus pneumoniae. Several models have been proposed to explain how primary respiratory
viral infections exacerbate secondary
bacterial disease, but the mechanistic explanations have been contradictory. In this study, mice were infected with S. pneumoniae at different days after primary
influenza A (X31)
virus infection. Our findings show that the induction of
type I interferons (IFNs) during a primary nonlethal influenza virus
infection is sufficient to promote a deadly S. pneumoniae
secondary infection. Moreover, mice deficient in
type I interferon receptor (IFNAR knockout [KO] mice) effectively cleared the secondary
bacterial infection from their lungs, increased the recruitment of neutrophils, and demonstrated an enhanced innate expression of
interleukin-17 (IL-17) relative to wild-type (WT) mice. Lung γδ T cells were responsible for almost all
IL-17 production, and their function is compromised during secondary S. pneumoniae
infection of WT but not IFNAR KO mice. Adoptive transfer of γδ T cells from IFNAR KO mice reduced the susceptibility to secondary S. pneumoniae
infection in the lung of WT mice. Altogether, our study highlights the importance of
type I interferon as a key master regulator that is exploited by opportunistic pathogens such as S. pneumoniae. Our findings may be utilized to design effective preventive and therapeutic strategies that may be beneficial for coinfected patients during
influenza epidemics.