Neutrophil extracellular traps may have a dual role in Pseudomonas aeruginosa keratitis
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ORIGINAL ARTICLE
Neutrophil extracellular traps may have a dual role in Pseudomonas aeruginosa keratitis Binbin Zhu 1 & Lu Zhang 1 & Kelan Yuan 1 & Xiaodan Huang 1 & Renjian Hu 1 & Xiuming Jin 1 Received: 14 April 2020 / Accepted: 26 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Pseudomonas aeruginosa (P. aeruginosa) keratitis is a sight-threatening and rapidly progressive corneal disease. Neutrophils and neutrophil extracellular traps (NETs) are widely thought to play a vital role in hosts’ immune defenses against bacteria, such as P. aeruginosa. The present study aimed to investigate the dynamics of the formation and the role of NETs in P. aeruginosa keratitis. First, scratched corneas of mice models were treated with 1 × 108 colony-forming units (CFU)/ml of P. aeruginosa suspension or normal saline (NS). Second, after 48 h postinfection, the infected corneas were treated with TobraDex, Tobrex, 0.1% dexamethasone, or NS four times a day, respectively. Clinical examination, hematoxylin and eosin (H&E) staining, immunofluorescence staining, scanning electron microscopy, and bacterial burden testing were performed on the corneas. Tobrex reduced neutrophil infiltration and corneal P. aeruginosa burden. Dexamethasone reduced NETs, bacterial burden, and severe neutrophil infiltration. TobraDex produced a greater reduction in the amount of neutrophils, NETs, and bacterial burden and the results of Tobrex-treated group were between them. These findings corresponded with the clinical findings that TobraDex- and Tobrex-treated mice exhibited slight corneal damage, while dexamethasone-treated mice exhibited very severe corneal damage. Cumulatively, our data suggest that NETs may play a dual role of infection control and corneal damage in P. aeruginosa keratitis. Furthermore, combination treatment targeting NET formation and bacteria may serve as a way of improving the clinical outcomes of bacterial keratitis. Keywords Neutrophil extracellular traps . P. aeruginosa keratitis . Dexamethasone . Tobramycin . Combination treatment
Introduction Neutrophils, as the first line of a host’s immune defense, fight infections by phagocytosis, degranulation, cytokine production, and neutrophil extracellular trap (NET) production. Bacteria and their metabolic products have been confirmed to induce NET formation [1–4]. The composition of NETs consists of decondensed chromatin decorated with many granular proteins, including histones, elastase, myeloperoxidase (MPO), and cathepsin G [5, 6]. Furthermore, NETs have an Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10096-020-04023-2) contains supplementary material, which is available to authorized users. * Xiuming Jin [email protected] 1
Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou 310009, China
opposing dual role in tissue homeostasis, in that they can locally restrain infections by trapping and killing bacteria [7]. It is well known that chro
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