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. The gene discussed is IFNB1; the disease is bacterial infectious disease.