Loss of T‐bet confers survival advantage to influenza–bacterial superinfection

The transcription factor, T‐bet, regulates type 1 inflammatory responses against a range of infections. Here, we demonstrate a previously unaddressed role of T‐bet, to influenza virus and bacterial superinfection. Interestingly, we found that T‐bet deficiency did not adversely affect the efficacy of viral clearance or recovery compared to wild‐type hosts. Instead, increased infiltration of neutrophils and production of Th17 cytokines (IL‐17 and IL‐22), in lungs of influenza virus‐infected T‐bet(−/−) mice, were correlated with survival advantage against subsequent infection by Streptococcus pneumoniae. Neutralization of IL‐17, but not IL‐22, in T‐bet(−/−) mice increased pulmonary bacterial load, concomitant with decreased neutrophil infiltration and reduced survival of T‐bet(−/−) mice. IL‐17 production by CD8(+), CD4(+) and γδ T cell types was identified to contribute to this protection against bacterial superinfection. We further showed that neutrophil depletion in T‐bet(−/−) lungs increased pulmonary bacterial burden. These results thus indicate that despite the loss of T‐bet, immune defences required for influenza viral clearance are fully functional, which in turn enhances protective type 17 immune responses against lethal bacterial superinfections.