IL27 and influenza: Since IL-27 is an important regulatory cytokine that can limit ongoing immune responses depending on context (Hunter & Kastelein 2012), we first examined the induction of IL-27 in vivo, and found that influenza infection elicited elevated levels of IL-27 and IL-27 peaked on day 5 and persisted to day 12 (Fig 3A), which correlated with the timing of high susceptibility to secondary S. pneumoniae infection on 5–7 days after primary influenza infection.