In this study, we focused on the impact of host airway microenvironment on bacterial infections and combined with the current hot topic of bacteria-virus co-infection, while verifying previous conclusions, we innovatively revealed that acidic microenvironment significantly promoted IFN-β production after P. aeruginosa infection and targeted knockout of IRF3 or IFNAR1 could reverse lung damage from P. aeruginosa infection that exacerbated by airway acidification. Here, IFNB1 is linked to coinfection.