Please use this identifier to cite or link to this item: https://doi.org/10.3389/fcimb.2017.00401
Title: Comparison of diabetic and non-diabetic human leukocytic responses to different capsule types of Klebsiella pneumoniae responsible for causing pyogenic liver abscess
Authors: Lee, I.R 
Sng, E 
Lee, K.-O 
Molton, J.S 
Chan, M
Kalimuddin, S 
Izharuddin, E
Lye, D.C 
Archuleta, S 
Gan, Y.-H 
Keywords: antibiotic agent
gamma interferon
glucose
hemoglobin A1c
interleukin 10
interleukin 12
interleukin 17
interleukin 1beta
interleukin 6
bacterial antigen
bacterial DNA
bacterial polysaccharide
capsular polysaccharide K1
chemokine
cytokine
gamma interferon
interleukin 12
peroxidase
tumor necrosis factor receptor 1
tumor necrosis factor receptor 2
virulence factor
Article
bacterial infection
bactericidal activity
controlled study
cytokine production
cytokine response
enzyme linked immunosorbent assay
extracellular trap
flow cytometry
glycemic control
human
human experiment
immunofluorescence microscopy
innate immunity
Klebsiella pneumoniae
leukocyte activation
non insulin dependent diabetes mellitus
nonhuman
peripheral blood mononuclear cell
phagocytosis
pyogenic liver abscess
adult
aged
bacterial capsule
blood
complication
immunology
Klebsiella infection
Klebsiella pneumoniae
metabolism
microbiology
middle aged
mononuclear cell
neutrophil
non insulin dependent diabetes mellitus
pathogenicity
pyogenic liver abscess
serum bactericidal activity
Adult
Aged
Antigens, Bacterial
Bacterial Capsules
Blood Bactericidal Activity
Chemokines
Cytokines
Diabetes Mellitus, Type 2
DNA, Bacterial
Extracellular Traps
Humans
Interferon-gamma
Interleukin-12
Klebsiella Infections
Klebsiella pneumoniae
Leukocytes, Mononuclear
Liver Abscess, Pyogenic
Middle Aged
Neutrophils
Peroxidase
Phagocytosis
Polysaccharides, Bacterial
Receptors, Tumor Necrosis Factor, Type I
Receptors, Tumor Necrosis Factor, Type II
Virulence Factors
Issue Date: 2017
Citation: Lee, I.R, Sng, E, Lee, K.-O, Molton, J.S, Chan, M, Kalimuddin, S, Izharuddin, E, Lye, D.C, Archuleta, S, Gan, Y.-H (2017). Comparison of diabetic and non-diabetic human leukocytic responses to different capsule types of Klebsiella pneumoniae responsible for causing pyogenic liver abscess. Frontiers in Cellular and Infection Microbiology 7 (SEP) : 401. ScholarBank@NUS Repository. https://doi.org/10.3389/fcimb.2017.00401
Abstract: The major risk factor for Klebsiella liver abscess (KLA) is type 2 diabetes mellitus (DM), but the immunological mechanisms involved in the increased susceptibility are poorly defined. We investigated the responses of neutrophils and peripheral blood mononuclear cells (PBMCs) to hypervirulent Klebsiella pneumoniae (hvKP), the causative agent of KLA. DNA and myeloperoxidase levels were elevated in the plasma of KLA patients compared to uninfected individuals indicating neutrophil activation, but diabetic status had no effect on these neutrophil extracellular trap (NET) biomarkers in both subject groups. Clinical hvKP isolates universally stimulated KLA patient neutrophils to produce NETs ex vivo, regardless of host diabetic status. Ability of representative capsule types (K1, K2, and non-K1/K2 strains) to survive intra- and extra-cellular killing by type 2 DM and healthy neutrophils was subsequently examined. Key findings were: (1) type 2 DM and healthy neutrophils exhibited comparable total, phagocytic, and NETs killing against hvKP, (2) phagocytic and NETs killing were equally effective against hvKP, and (3) hypermucoviscous K1 and K2 strains were more resistant to total, phagocytic, and NETs killing compared to the non-mucoviscous, non-K1/K2 strain. The cytokine response and intracellular killing ability of type 2 DM as well as healthy PBMCs upon encounter with the different capsule types was also examined. Notably, the IL-12-IFNγ axis and its downstream chemokines MIG, IP-10, and RANTES were produced at slightly lower levels by type 2 DM PBMCs than healthy PBMCs in response to representative K1 and non-K1/K2 strains. Furthermore, type 2 DM PBMCs have a mild defect in its ability to control hvKP replication relative to healthy PBMCs. In summary, our work demonstrates that type 2 DM does not overtly impact neutrophil intra- and extra-cellular killing of hvKP, but may influence cytokine/chemokine production and intracellular killing by PBMCs. © 2017 Lee, Sng, Lee, Molton, Chan, Kalimuddin, Izharuddin, Lye, Archuleta and Gan.
Source Title: Frontiers in Cellular and Infection Microbiology
URI: https://scholarbank.nus.edu.sg/handle/10635/176080
ISSN: 2235-2988
DOI: 10.3389/fcimb.2017.00401
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