Pseudomonas aeruginosa is a common gram-negative bacterium that usually causes nosocomial infection. The main pathogenicity of P. aeruginosa is caused by its virulence factors. PA2146 is reported to be a potential virulence-regulating gene and is highly expressed in the biofilms of P. aeruginosa. However, the effect of PA2146 mutant (PAO1ΔPA2146) on the macrophage immune response and murine models has not been reported. In the present study, PA2146 knockout was performed by homologous recombination. We found that PAO1ΔPA2146 stimulation significantly increased pyocyanin production but inhibited interleukin-6 secretion by neutrophils compared to PAO1 stimulation. In addition, PAO1ΔPA2146 treatment significantly inhibited cytokine production in macrophages independent of cell killing. In an acute pneumonia murine infection model, treatment with P. aeruginosa infected with PAO1ΔPA2146 inhibited cytokine secretion in the lungs but increased the infiltration of inflammatory cells compared to the wild-type group. The paradoxical results indicate that PA2146 deletion may also increase the production of virulence factors other than pyocyanin, which may not only increase inflammatory cell infiltration in the lungs but also lead to immune cells “shock.” Overall, our findings suggest that PA2146 could serve as a P. aeruginosa virulence-regulating gene that regulates its macrophage and host immune response.

铜绿假单胞菌是常见的革兰氏阴性细菌，通常引起医院感染。的主要致病性铜绿假单胞菌 是由其毒力因素引起的。 PA2146 据报道是潜在的毒力调节基因，并在其生物膜中高表达。 铜绿假单胞菌。但是，效果PA2146 突变体（PAO1ΔPA2146）关于巨噬细胞的免疫反应和鼠模型尚未见报道。在目前的研究中，PA2146通过同源重组进行敲除。我们发现PAO1ΔPA2146与PAO1刺激相比，刺激显着增加了卵黄蛋白的产量，但抑制了中性粒细胞分泌白介素6的能力。另外，PAO1ΔPA2146这种治疗显着抑制了巨噬细胞中细胞因子的产生，而与细胞杀伤无关。在急性肺炎鼠感染模型中，铜绿假单胞菌 被PAO1Δ感染PA2146与野生型组相比，它抑制了肺中细胞因子的分泌，但增加了炎性细胞的浸润。矛盾的结果表明PA2146缺失还可能会增加除绿脓素以外的毒力因子的产生，这不仅会增加肺部炎症细胞的浸润，还会导致免疫细胞“休克”。总体而言，我们的发现表明PA2146 可以作为一个 铜绿假单胞菌 调节巨噬细胞和宿主免疫反应的毒力调节基因。