Antibiotic use during influenza infection augments lung eosinophils that impair immunity against secondary bacterial pneumonia.

Marilia Sanches Santos Rizzo Zuttion,Tanyalak Parimon,Stephanie A Bora,Changfu Yao,Katherine Lagree,Catherine A Gao,Richard G Wunderink,Georgios D Kitsios,Alison Morris,Yingze Zhang,Bryan J McVerry,Matthew E Modes,Alberto M Marchevsky,Barry R Stripp,Christopher M Soto,Ying Wang,Kimberly Merene,Silvia Cho,Blandine L Victor,Ivan Vujkovic-Cvijin,Suman Gupta,Suzanne Cassel,Fayyaz S Sutterwala,Suzanne Devkota,David M Underhill,Peter Chen
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Abstract

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 antibiotic treatment during influenza infection causes a fungal dysbiosis that drive lung eosinophilia and impair MRSA clearance. Finally, we evaluated three cohorts of hospitalized patients and found 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.
流感感染期间使用抗生素会增加肺部嗜酸性粒细胞,从而损害对继发性细菌性肺炎的免疫力。
流感感染后的一个主要致死原因是继发细菌性肺炎。在没有细菌超级感染的情况下,不建议使用抗菌疗法,但这已成为呼吸道病毒性疾病患者的常见临床实践。在一个小鼠模型中,我们发现在流感感染期间使用抗生素会损害肺部先天性免疫防御系统,使其无法应对耐甲氧西林金黄色葡萄球菌(MRSA)的二次挑战。抗生素会增加肺嗜酸性粒细胞,而嗜酸性粒细胞会通过释放主要碱性蛋白抑制巨噬细胞的功能。此外,我们还证明流感感染期间的抗生素治疗会导致真菌菌群失调,从而引起肺嗜酸性粒细胞增多并影响 MRSA 的清除。最后,我们对三组住院患者进行了评估,发现嗜酸性粒细胞与抗生素使用、全身炎症和预后恶化呈正相关。总之,我们的工作证明了流感感染期间抗生素治疗的有害影响,这种影响会通过肺部嗜酸性粒细胞的招募产生有害的免疫学后果,从而增加继发细菌感染的风险。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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