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抗铜绿假单胞菌IgY抗体诱导人多形核中性粒细胞中特定细菌的聚集和内化。

Anti-Pseudomonas aeruginosa IgY Antibodies Induce Specific Bacterial Aggregation and Internalization in Human Polymorphonuclear Neutrophils.

作者信息

Thomsen K, Christophersen L, Bjarnsholt T, Jensen P Ø, Moser C, Høiby N

机构信息

Department of Clinical Microbiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Department of Clinical Microbiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark Department of International Health, Immunology and Microbiology, Faculty of Health Sciences University of Copenhagen, Copenhagen, Denmark.

出版信息

Infect Immun. 2015 Jul;83(7):2686-93. doi: 10.1128/IAI.02970-14. Epub 2015 Apr 20.

Abstract

Polymorphonuclear neutrophils (PMNs) are essential cellular constituents in the innate host response, and their recruitment to the lungs and subsequent ubiquitous phagocytosis controls primary respiratory infection. Cystic fibrosis pulmonary disease is characterized by progressive pulmonary decline governed by a persistent, exaggerated inflammatory response dominated by PMNs. The principal contributor is chronic Pseudomonas aeruginosa biofilm infection, which attracts and activates PMNs and thereby is responsible for the continuing inflammation. Strategies to prevent initial airway colonization with P. aeruginosa by augmenting the phagocytic competence of PMNs may postpone the deteriorating chronic biofilm infection. Anti-P. aeruginosa IgY antibodies significantly increase the PMN-mediated respiratory burst and subsequent bacterial killing of P. aeruginosa in vitro. The mode of action is attributed to IgY-facilitated formation of immobilized bacteria in aggregates, as visualized by fluorescence microscopy and the induction of increased bacterial hydrophobicity. Thus, the present study demonstrates that avian egg yolk immunoglobulins (IgY) targeting P. aeruginosa modify bacterial fitness, which enhances bacterial killing by PMN-mediated phagocytosis and thereby may facilitate a rapid bacterial clearance in airways of people with cystic fibrosis.

摘要

多形核中性粒细胞(PMNs)是先天性宿主反应中重要的细胞成分,它们募集到肺部并随后广泛进行吞噬作用,从而控制原发性呼吸道感染。囊性纤维化肺部疾病的特征是肺部进行性衰退,其由以PMNs为主导的持续、过度炎症反应所控制。主要促成因素是慢性铜绿假单胞菌生物膜感染,它吸引并激活PMNs,从而导致持续炎症。通过增强PMNs的吞噬能力来预防铜绿假单胞菌初始气道定植的策略,可能会推迟慢性生物膜感染的恶化。抗铜绿假单胞菌IgY抗体在体外可显著增强PMN介导的呼吸爆发以及随后对铜绿假单胞菌的细菌杀伤作用。其作用方式归因于IgY促进细菌聚集形成固定化细菌,这可通过荧光显微镜观察到,并且还能诱导细菌疏水性增加。因此,本研究表明,靶向铜绿假单胞菌的禽蛋黄免疫球蛋白(IgY)可改变细菌适应性,增强PMN介导的吞噬作用对细菌的杀伤,从而可能有助于快速清除囊性纤维化患者气道中的细菌。

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