A leading cause of mortality after influenza infection is the development of a secondary bacterial pneumonia. In the absence of a bacterial superinfection, prescribing antibacterial therapies is not indicated but has become a common clinical practice for those presenting with a respiratory viral illness. In a murine model, we found that antibiotic use during influenza infection impaired the lung innate immunologic defenses toward a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA). Antibiotics augment lung eosinophils, which have inhibitory effects on macrophage function through the release of major basic protein. Moreover, we demonstrated that antibiotic treatment during influenza infection caused a fungal dysbiosis that drove lung eosinophilia and impaired MRSA clearance. Finally, we evaluated 3 cohorts of hospitalized patients and found that eosinophils positively correlated with antibiotic use, systemic inflammation, and worsened outcomes. Altogether, our work demonstrates a detrimental effect of antibiotic treatment during influenza infection that has harmful immunologic consequences via recruitment of eosinophils to the lungs, thereby increasing the risk of developing a secondary bacterial infection.

中文翻译：

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流感感染期间使用抗生素会增加肺嗜酸性粒细胞，从而损害对继发性细菌性肺炎的免疫力


流感感染后死亡的主要原因是继发性细菌性肺炎的发展。在没有细菌重叠感染的情况下，不需要开具抗菌疗法，但已成为呼吸道病毒性疾病患者的常见临床实践。在小鼠模型中，我们发现流感感染期间使用抗生素会损害肺先天免疫防御能力，以应对耐甲氧西林金黄色葡萄球菌 （MRSA） 的继发性攻击。抗生素可增强肺嗜酸性粒细胞，肺嗜酸性粒细胞通过释放主要碱性蛋白对巨噬细胞功能产生抑制作用。此外，我们证明流感感染期间的抗生素治疗会导致真菌菌群失调，从而导致肺嗜酸性粒细胞增多和 MRSA 清除受损。最后，我们评估了 3 组住院患者，发现嗜酸性粒细胞与抗生素使用、全身炎症和恶化的结果呈正相关。总而言之，我们的工作证明了流感感染期间抗生素治疗的有害作用，通过嗜酸性粒细胞募集到肺部而产生有害的免疫后果，从而增加发生继发性细菌感染的风险。