Neutrophil extracellular traps (NETs)-mediated killing of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) are impaired in patients with diabetes mellitus

Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) have been reported in recent years across Asian countries and pose a serious threat to public health. Neutrophils represent the first line of defense against numerous infectious pathogens, such as CR-hvKP. Neutrophil extracellular tr...

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Autores principales:	Longyang Jin, Yudong Liu, Chendi Jing, Ruobing Wang, Qi Wang, Hui Wang
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2020
Materias:	neutrophil extracellular traps (nets) carbapenem-resistant hypervirulent klebsiella pneumoniae (cr-hvkp) type 2 diabetes mellitus (t2d) antimicrobial activity innate immunity Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/629d5b7b6f734a398d0cc85f95c684d6
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spelling	oai:doaj.org-article:629d5b7b6f734a398d0cc85f95c684d62021-11-17T14:21:58ZNeutrophil extracellular traps (NETs)-mediated killing of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) are impaired in patients with diabetes mellitus2150-55942150-560810.1080/21505594.2020.1809325https://doaj.org/article/629d5b7b6f734a398d0cc85f95c684d62020-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2020.1809325https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) have been reported in recent years across Asian countries and pose a serious threat to public health. Neutrophils represent the first line of defense against numerous infectious pathogens, such as CR-hvKP. Neutrophil extracellular traps (NETs) constitute one of the major antimicrobial defense mechanisms in neutrophils against invading pathogens, especially against hvKP. Interestingly, previous studies have demonstrated that patients with type 2 diabetes mellitus (T2D) display elevated levels of NETosis but are vulnerable to infections caused by hvKP. The discrepancy propels us to investigate the role of NETs in hvKP infections in the context of T2D. By utilizing a clinical-derived CR-hvKP strain and a combination of NETs complex detection, phagocytosis testing, NETs killing assay and immunofluorescence, and scanning electron microscope assays, we identified defective NETs-mediated killing of CR-hvKP strain in patients with T2D. Specifically, we show that the impaired NETs-mediated killing in T2D is not due to the decreased NETs formation, as the neutrophils isolated from T2D patients exhibited enhanced NETs formation compared to healthy controls. Further, we demonstrate that the reduced NETs activity does not result from the trapping failure of CR-hvKP, but likely associated with the deficient surface damage conferred by the NETs of T2D patients. Our data provide a novel insight into the defective innate immune response against CR-hvKP in T2D.Longyang JinYudong LiuChendi JingRuobing WangQi WangHui WangTaylor & Francis Grouparticleneutrophil extracellular traps (nets)carbapenem-resistant hypervirulent klebsiella pneumoniae (cr-hvkp)type 2 diabetes mellitus (t2d)antimicrobial activityinnate immunityInfectious and parasitic diseasesRC109-216ENVirulence, Vol 11, Iss 1, Pp 1122-1130 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	neutrophil extracellular traps (nets) carbapenem-resistant hypervirulent klebsiella pneumoniae (cr-hvkp) type 2 diabetes mellitus (t2d) antimicrobial activity innate immunity Infectious and parasitic diseases RC109-216
spellingShingle	neutrophil extracellular traps (nets) carbapenem-resistant hypervirulent klebsiella pneumoniae (cr-hvkp) type 2 diabetes mellitus (t2d) antimicrobial activity innate immunity Infectious and parasitic diseases RC109-216 Longyang Jin Yudong Liu Chendi Jing Ruobing Wang Qi Wang Hui Wang Neutrophil extracellular traps (NETs)-mediated killing of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) are impaired in patients with diabetes mellitus
description	Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) have been reported in recent years across Asian countries and pose a serious threat to public health. Neutrophils represent the first line of defense against numerous infectious pathogens, such as CR-hvKP. Neutrophil extracellular traps (NETs) constitute one of the major antimicrobial defense mechanisms in neutrophils against invading pathogens, especially against hvKP. Interestingly, previous studies have demonstrated that patients with type 2 diabetes mellitus (T2D) display elevated levels of NETosis but are vulnerable to infections caused by hvKP. The discrepancy propels us to investigate the role of NETs in hvKP infections in the context of T2D. By utilizing a clinical-derived CR-hvKP strain and a combination of NETs complex detection, phagocytosis testing, NETs killing assay and immunofluorescence, and scanning electron microscope assays, we identified defective NETs-mediated killing of CR-hvKP strain in patients with T2D. Specifically, we show that the impaired NETs-mediated killing in T2D is not due to the decreased NETs formation, as the neutrophils isolated from T2D patients exhibited enhanced NETs formation compared to healthy controls. Further, we demonstrate that the reduced NETs activity does not result from the trapping failure of CR-hvKP, but likely associated with the deficient surface damage conferred by the NETs of T2D patients. Our data provide a novel insight into the defective innate immune response against CR-hvKP in T2D.
format	article
author	Longyang Jin Yudong Liu Chendi Jing Ruobing Wang Qi Wang Hui Wang
author_facet	Longyang Jin Yudong Liu Chendi Jing Ruobing Wang Qi Wang Hui Wang
author_sort	Longyang Jin
title	Neutrophil extracellular traps (NETs)-mediated killing of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) are impaired in patients with diabetes mellitus
title_short	Neutrophil extracellular traps (NETs)-mediated killing of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) are impaired in patients with diabetes mellitus
title_full	Neutrophil extracellular traps (NETs)-mediated killing of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) are impaired in patients with diabetes mellitus
title_fullStr	Neutrophil extracellular traps (NETs)-mediated killing of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) are impaired in patients with diabetes mellitus
title_full_unstemmed	Neutrophil extracellular traps (NETs)-mediated killing of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) are impaired in patients with diabetes mellitus
title_sort	neutrophil extracellular traps (nets)-mediated killing of carbapenem-resistant hypervirulent klebsiella pneumoniae (cr-hvkp) are impaired in patients with diabetes mellitus
publisher	Taylor & Francis Group
publishDate	2020
url	https://doaj.org/article/629d5b7b6f734a398d0cc85f95c684d6
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Neutrophil extracellular traps (NETs)-mediated killing of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) are impaired in patients with diabetes mellitus

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