L-PaF/E/ME/BECC immunized mice lungs prepare itself for impending Pseudomonas aeruginosa infection by interferon controlled immune and stromal cell interactions

Pseudomonas aeruginosa (Pa) is a Gram-negative respiratory pathogen that causes life threatening pneumonia in immunocompromised individuals, however, it can also infect immunocompetent patients in hospital settings. No licensed vaccine is available against Pa. It is becoming difficult to treat Pa infections due to increasing antibiotic resistance and the rise of multidrug resistant (MDR) strains. In this scenario, a prophylactic vaccine is desirable which may curb Pa infection from occurring. Previously, we demonstrated the effectiveness of a type III secretion system-based Pa vaccine platform called L-PaF. Here we reveal the cell types required to construct a protective lung microenvironment by the help of various immune pathways and genes after vaccination with L-PaF/E/ME/BECC. Both adaptive and innate immune responses found to play roles to mount anti-Pa response, namely, conventional (??) and unconventional (??? T cells, along with effector cells such as macrophages and neutrophils. Moreover, antigen presentation was found to play a pivotal role by the help of interferon system (types I and II). This was further proved using interferon receptor knock out mice. Lung homeostasis after infection is soon restored in immunized animals by stromal and immune cells by the help of a proper cytokine, chemokine milieu which was missing and is disarray in control animals. Collectively, immunized animals' lungs were more “educated and prepared” where the lung microenvironment slows down or stops the onset of infection by the help of innate and adaptive cells whereas, lungs of naïve animals were far more prone to the disease because their lungs are overwhelmed when infected, causing massive lung burden.