GSE126622
BCL6 modulates tissue neutrophil survival and exacerbates pulmonary inflammation following influenza infection
Epidemics of influenza virus are of great challenges to the public concern. The lung inflammation and injury caused by excessive inflammatory cell infiltration into the lungs and overproduction of inflammatory mediators are major consequences during influenza virus infection. Neutrophils are vital for anti-microbial defense. However, the roles of neutrophils during viral infections are less clear. Furthermore, the molecular regulation of neutrophil fate and function at the viral infected sites is largely elusive. We found that BCL6 deficiency in neutrophils, but not in monocytes nor lung macrophages, attenuated host inflammation and morbidity following influenza infection. Mechanistically, BCL6 bound to the neutrophil gene loci involved in cellular apoptosis specifically at the site of infection. As such, BCL6 disruption resulted in increased expression of apoptotic genes in neutrophils in the respiratory tract, but not in the circulation nor bone marrow. Consequently, BCL6 deficiency promoted tissue neutrophil apoptosis. Our results have revealed a previously unappreciated role of BCL6 in modulating neutrophil apoptosis at the site of infection for the regulation of host disease development following viral infection. Overall design: Neutrophils were flow sorted based on their surface expression of CD11b and Ly6G from total lung cells of MRP8-Cre Bcl6 or Bcl6 fl/fl mice at day 6 post influenza virus infection. Total RNA was isolated and RNA-seq was performed.