Dopamine promotesKlebsiella quasivariicolaproliferation and inflammatory response in the presence of macrophages

Abstract

AbstractKlebsiella quasivariicolawas a novel strain ofKlebsiellaspecies and had potential pathogenicity. Our previously studies showed dopamine, one of the most commonly used rescue drugs for critically ill patients, had clear effects on the growth ofK. quasivariicolain culture medium, however, its effects on host immune system were ignored. Therefore, in consideration of the host immunity, the interactions ofK. quasivariicola, dopamine and macrophages were explored. In this study, RAW264.7 cells and C57/BL6 mice were infected withK. quasivariicola, and the bacterial growth in macrophage, the production of inflammatory cytokines and the pathological changes of mice lung were detected, in the absence or presence of dopamine. Our results showed dopamine inhibited theK. quasivariicolagrowth in medium, but promoted the bacterial growth whenK. quasivariicolawas co-cultured with macrophages; The expression of proinflammatory cytokines inK. quasivariicolainfected RAW 264.7 were increased, while a sharp rise was observed with the addition of dopamine; Infection ofK. quasivariicolato mice induced an inflammatory response and lung injury, which were exacerbated by dopamine administration. It can be concluded that dopamine administration resulted in a significantly increase ofK. quasivariicolaburdens in the presence of macrophage, consequently, aggravated the inflammatory response and inflammatory injury.ImportanceDopamine is one of the most commonly used rescue drugs for critically ill patients. Here we indicatedK. quasivariicolawas a potential pathogen of pulmonary infection, and dopamine significantly increased the proliferation ofK. quasivariicolawhen exposed to macrophage, subsequently result in severe inflammatory response and inflammatory injury. We also proposed anin vitromodel of microbes-drugs-host immune cells that could better mimicin vivoenvironment and more suitable for the studies of inhibitor screening. This fundamental work had contributed to the present understanding of the crosstalk between pathogen, dopamine and host immune cells. Furthermore, our data showed dopamine was one of the risk factors for patients withK. quasivariicolainfection, which provided a basis for clinical precision medicine.