Pseudomonas aeruginosa Induces Interferon-beta Production to Promote Intracellular Survival

Pseudomonas aeruginosa (PA) is known as one kind of extracellular pathogens. However, more evidence showed that PA encounters the intracellular environment in different mammalian cell types. Little is known of innate immune factors modulating intracellular PA survival. In the present study, we proposed that interferon-beta (IFN-beta) is beneficial to the survival of PA in the cytoplasm of macrophages. Furthermore, we found that interleukin-1 beta (IL-1 beta) induced by PA suppresses IFN-beta response driven by the cGAS-STING-TBK1 pathway. Mechanistically, IL-1 beta decreased the production of cyclic GMP-AMP (cGAMP) by activating AKT kinase. cGAMP is necessarily sufficient to stimulate the transcription of IFN-beta via the STING adaptor-TBK1 kinase-IRF3 transcription factor axis. Thus, our findings uncovered a novel module for PA intracellular survival involving IFN-beta production restricted by IL-1 beta and provided a strong rationale for a potential clinical strategy against pulmonary PA infection patients. IMPORTANCE The link between innate immunity and intracellular Pseudomonas aeruginosa is unclear. Our studies illuminated the role of interferon-beta (IFN-beta) in remote intracellular PA infection. Furthermore, our experimental evidence also indicated that IL-1 beta is a negative regulator of IFN-beta production and, in particular, P. aeruginosa infection. The inhibition of IFN-beta may be used as a potential therapeutic method against pulmonary PA infection. IMPORTANCE The link between innate immunity and intracellular Pseudomonas aeruginosa is unclear. Our studies illuminated the role of interferon-beta (IFN-beta) in remote intracellular PA infection. Furthermore, our experimental evidence also indicated that IL-1 beta is a negative regulator of IFN-beta production and, in particular, P. aeruginosa infection. The inhibition of IFN-beta may be used as a potential therapeutic method against pulmonary PA infection.