Dopamine promotes Klebsiella quasivariicola proliferation and inflammatory response in the presence of macrophages

Yan, Q.; Li, X.; Cheng, L.; Liu, X.; Wang, X.; Li, R.; Fan, S.; Ma, T.; Ma, Y.; Kang, J.

doi:10.1101/2023.01.28.526064

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bioRxiv · 10.1101/2023.01.28.526064

Dopamine promotes Klebsiella quasivariicola proliferation and inflammatory response in the presence of macrophages

Yan, Q.·Li, X.·Cheng, L.·Liu, X.·Wang, X.·Li, R.·Fan, S.·Ma, T.·Ma, Y.·Kang, J.

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Abstract

Klebsiella quasivariicola was a novel strain of Klebsiella species 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 of K. quasivariicola in culture medium, however, its effects on host immune system were ignored. Therefore, in consideration of the host immunity, the interactions of K. quasivariicola, dopamine and macrophages were explored. In this study, RAW264.7 cells and C57/BL6 mice were infected with K. 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 the K. quasivariicola growth in medium, but promoted the bacterial growth when K. quasivariicola was co-cultured with macrophages; The expression of proinflammatory cytokines in K. quasivariicola infected RAW 264.7 were increased, while a sharp rise was observed with the addition of dopamine; Infection of K. quasivariicola to 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 of K. quasivariicola burdens 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 indicated K. quasivariicola was a potential pathogen of pulmonary infection, and dopamine significantly increased the proliferation of K. quasivariicola when exposed to macrophage, subsequently result in severe inflammatory response and inflammatory injury. We also proposed an in vitro model of microbes-drugs-host immune cells that could better mimic in vivo environment 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 with K. quasivariicola infection, which provided a basis for clinical precision medicine.

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Yan, Q., Li, X., Cheng, L., Liu, X., Wang, X., Li, R., Fan, S., Ma, T., Ma, Y., Kang, J.. 2023-01-29. Dopamine promotes Klebsiella quasivariicola proliferation and inflammatory response in the presence of macrophages. https://doi.org/10.1101/2023.01.28.526064

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