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C/EBPε mediates nicotinamide-enhanced clearance of Staphylococcus aureus in mice

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C/EBPε mediates nicotinamide-enhanced clearance of Staphylococcus aureus in mice. / Kyme, Pierre; Thoennissen, Nils H; Tseng, Ching Wen; Thoennissen, Gabriela B; Wolf, Andrea J; Shimada, Kenichi; Krug, Utz O; Lee, Kunik; Müller-Tidow, Carsten; Berdel, Wolfgang E; Hardy, W David; Gombart, Adrian F; Koeffler, H Phillip; Liu, George Y.

in: J CLIN INVEST, Jahrgang 122, Nr. 9, 09.2012, S. 3316-29.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Kyme, P, Thoennissen, NH, Tseng, CW, Thoennissen, GB, Wolf, AJ, Shimada, K, Krug, UO, Lee, K, Müller-Tidow, C, Berdel, WE, Hardy, WD, Gombart, AF, Koeffler, HP & Liu, GY 2012, 'C/EBPε mediates nicotinamide-enhanced clearance of Staphylococcus aureus in mice', J CLIN INVEST, Jg. 122, Nr. 9, S. 3316-29. https://doi.org/10.1172/JCI62070

APA

Kyme, P., Thoennissen, N. H., Tseng, C. W., Thoennissen, G. B., Wolf, A. J., Shimada, K., Krug, U. O., Lee, K., Müller-Tidow, C., Berdel, W. E., Hardy, W. D., Gombart, A. F., Koeffler, H. P., & Liu, G. Y. (2012). C/EBPε mediates nicotinamide-enhanced clearance of Staphylococcus aureus in mice. J CLIN INVEST, 122(9), 3316-29. https://doi.org/10.1172/JCI62070

Vancouver

Kyme P, Thoennissen NH, Tseng CW, Thoennissen GB, Wolf AJ, Shimada K et al. C/EBPε mediates nicotinamide-enhanced clearance of Staphylococcus aureus in mice. J CLIN INVEST. 2012 Sep;122(9):3316-29. https://doi.org/10.1172/JCI62070

Bibtex

@article{6c2ae92710ec4a35bada010990e947bd,
title = "C/EBPε mediates nicotinamide-enhanced clearance of Staphylococcus aureus in mice",
abstract = "The myeloid-specific transcription factor, CCAAT/enhancer-binding protein ε (C/EBPε) is a critical mediator of myelopoiesis. Mutation of this gene is responsible for neutrophil-specific granule deficiency in humans, a condition that confers susceptibility to Staphylococcus aureus infection. We found that C/EBPε-deficient mice are severely affected by infection with S. aureus, and C/EBPε deficiency in neutrophils contributes to the infectious phenotype. Conversely, exposure to the epigenetic modulator nicotinamide (vitamin B3) increased expression of C/EBPε in WT myeloid cells. Further, nicotinamide increased the activity of C/EBPε and select downstream antimicrobial targets, particularly in neutrophils. In a systemic murine infection model as well as in murine and human peripheral blood, nicotinamide enhanced killing of S. aureus by up to 1,000 fold but had no effect when administered to either C/EBPε-deficient mice or mice depleted of neutrophils. Nicotinamide was efficacious in both prophylactic and therapeutic settings. Our findings suggest that C/EBPε is an important target to boost killing of bacteria by the innate immune system.",
keywords = "Acetylation, Animals, Anti-Bacterial Agents, CCAAT-Enhancer-Binding Proteins, Cells, Cultured, Gene Expression, Gene Expression Regulation, Histones, Humans, Immunity, Innate, Macrophages, Mice, Mice, Knockout, Microbial Viability, Neutrophils, Niacinamide, Promoter Regions, Genetic, Staphylococcal Skin Infections, Staphylococcus aureus",
author = "Pierre Kyme and Thoennissen, {Nils H} and Tseng, {Ching Wen} and Thoennissen, {Gabriela B} and Wolf, {Andrea J} and Kenichi Shimada and Krug, {Utz O} and Kunik Lee and Carsten M{\"u}ller-Tidow and Berdel, {Wolfgang E} and Hardy, {W David} and Gombart, {Adrian F} and Koeffler, {H Phillip} and Liu, {George Y}",
year = "2012",
month = sep,
doi = "10.1172/JCI62070",
language = "English",
volume = "122",
pages = "3316--29",
journal = "J CLIN INVEST",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "9",

}

RIS

TY - JOUR

T1 - C/EBPε mediates nicotinamide-enhanced clearance of Staphylococcus aureus in mice

AU - Kyme, Pierre

AU - Thoennissen, Nils H

AU - Tseng, Ching Wen

AU - Thoennissen, Gabriela B

AU - Wolf, Andrea J

AU - Shimada, Kenichi

AU - Krug, Utz O

AU - Lee, Kunik

AU - Müller-Tidow, Carsten

AU - Berdel, Wolfgang E

AU - Hardy, W David

AU - Gombart, Adrian F

AU - Koeffler, H Phillip

AU - Liu, George Y

PY - 2012/9

Y1 - 2012/9

N2 - The myeloid-specific transcription factor, CCAAT/enhancer-binding protein ε (C/EBPε) is a critical mediator of myelopoiesis. Mutation of this gene is responsible for neutrophil-specific granule deficiency in humans, a condition that confers susceptibility to Staphylococcus aureus infection. We found that C/EBPε-deficient mice are severely affected by infection with S. aureus, and C/EBPε deficiency in neutrophils contributes to the infectious phenotype. Conversely, exposure to the epigenetic modulator nicotinamide (vitamin B3) increased expression of C/EBPε in WT myeloid cells. Further, nicotinamide increased the activity of C/EBPε and select downstream antimicrobial targets, particularly in neutrophils. In a systemic murine infection model as well as in murine and human peripheral blood, nicotinamide enhanced killing of S. aureus by up to 1,000 fold but had no effect when administered to either C/EBPε-deficient mice or mice depleted of neutrophils. Nicotinamide was efficacious in both prophylactic and therapeutic settings. Our findings suggest that C/EBPε is an important target to boost killing of bacteria by the innate immune system.

AB - The myeloid-specific transcription factor, CCAAT/enhancer-binding protein ε (C/EBPε) is a critical mediator of myelopoiesis. Mutation of this gene is responsible for neutrophil-specific granule deficiency in humans, a condition that confers susceptibility to Staphylococcus aureus infection. We found that C/EBPε-deficient mice are severely affected by infection with S. aureus, and C/EBPε deficiency in neutrophils contributes to the infectious phenotype. Conversely, exposure to the epigenetic modulator nicotinamide (vitamin B3) increased expression of C/EBPε in WT myeloid cells. Further, nicotinamide increased the activity of C/EBPε and select downstream antimicrobial targets, particularly in neutrophils. In a systemic murine infection model as well as in murine and human peripheral blood, nicotinamide enhanced killing of S. aureus by up to 1,000 fold but had no effect when administered to either C/EBPε-deficient mice or mice depleted of neutrophils. Nicotinamide was efficacious in both prophylactic and therapeutic settings. Our findings suggest that C/EBPε is an important target to boost killing of bacteria by the innate immune system.

KW - Acetylation

KW - Animals

KW - Anti-Bacterial Agents

KW - CCAAT-Enhancer-Binding Proteins

KW - Cells, Cultured

KW - Gene Expression

KW - Gene Expression Regulation

KW - Histones

KW - Humans

KW - Immunity, Innate

KW - Macrophages

KW - Mice

KW - Mice, Knockout

KW - Microbial Viability

KW - Neutrophils

KW - Niacinamide

KW - Promoter Regions, Genetic

KW - Staphylococcal Skin Infections

KW - Staphylococcus aureus

U2 - 10.1172/JCI62070

DO - 10.1172/JCI62070

M3 - SCORING: Journal article

C2 - 22922257

VL - 122

SP - 3316

EP - 3329

JO - J CLIN INVEST

JF - J CLIN INVEST

SN - 0021-9738

IS - 9

ER -