Abstract
Pseudomonas aeruginosa infection continues to be a major threat to global public health, and new safe and efficacious vaccines are needed for prevention of infections caused by P. aeruginosa. X-ray irradiation has been used to prepare whole-cell inactivated vaccines against P. aeruginosa infection. However, the immunological mechanisms of X-ray-inactivated vaccines are still unclear and require further investigation. Our previous study found that an X-ray-inactivated whole-cell vaccine could provide protection against P. aeruginosa by boosting T cells. The aim of the present study was to further explore the immunological mechanisms of the vaccine. Herein, P. aeruginosa PAO1, a widely used laboratory strain, was utilized to prepare the vaccine, and we found nucleic acids and 8-hydroxyguanosine in the supernatant of X-ray-inactivated PAO1 (XPa). By detecting CD86, CD80, and MHCII expression, we found that XPa fostered dentritic cell (DC) maturation by detecting. XPa stimulated the cGAS-STING pathway as well as Toll-like receptors in DCs in vitro, and DC finally underwent apoptosis and pyroptosis after XPa stimulation. In addition, DC stimulated by XPa induced CD8+ T-cell proliferation in vitro and generated immunologic memory in vivo. Moreover, XPa vaccination induced both Th1 and Th2 cytokine responses in mice and reduced the level of inflammatory factors during infection. XPa protected mice in pneumonia models from infection with PAO1 or multidrug-resistant clinical isolate W9. Chronic obstructive pulmonary disease (COPD) mice immunized with XPa could resist PAO1 infection. Therefore, a new mechanism of an X-ray-inactivated whole-cell vaccine against P. aeruginosa infection was discovered in this study.
Highlights
Pseudomonas aeruginosa (P. aeruginosa) infection is a major threat to global public health
X-ray irradiation induced nucleic acid release of PAO1 We conducted transmission electron microscopy to observe the shape of PAO1 after X-ray irradiation
Our previous study showed that X-ray irradiation induced nucleic acid release of PAO1.18 X-rays induced the production of the reactive form of oxygen, which causes oxidative damage to nucleic acids.[31]
Summary
Pseudomonas aeruginosa (P. aeruginosa) infection is a major threat to global public health. With the capacity to form concomitant biofilms,[9] which (i) shield bacteria from host immunity[10] and (ii) subvert the innate immune system through host cells,[11] the treatment of P. aeruginosa infection faces greater challenges
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