Involvement of matrix metalloproteinases in chronic Q fever

A.F.M. Jansen, T. Schoffelen, J. Textoris, J.L. Mege, C.P. Bleeker-Rovers, H.I.J. Roest, P.C. Wever, L.A.B. Joosten, M.G. Netea, E. van de Vosse, M. van Deuren

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Abstract

Objectives: Chronic Q fever is a persistent infection with the intracellular Gram-negative bacterium Coxiella burnetii, which can lead to complications of infected aneurysms. Matrix metalloproteinases (MMPs) cleave extracellular matrix and are involved in infections as well as aneurysms. We aimed to study the role of MMPs in the pathogenesis of chronic Q fever. Methods: We investigated gene expression of MMPs through microarray analysis and MMP production with ELISA in C. burnetii-stimulated peripheral blood mononuclear cells (PBMCs) of patients with chronic Q fever and healthy controls. Twenty single nucleotide polymorphisms (SNPs) of MMP and tissue inhibitor of MMP genes were genotyped in 139 patients with chronic Q fever and 220 controls with similar cardiovascular co-morbidity. Additionally, circulating MMPs levels in patients with chronic Q fever were compared with those in cardiovascular controls with and without a history of past Q fever. Results: In healthy controls, the MMP pathway involving four genes (MMP1, MMP7, MMP10, MMP19) was significantly up-regulated in C. burnetii-stimulated but not in Escherichia coli lipopolysaccharide -stimulated PBMCs. Coxiella burnetii induced MMP-1 and MMP-9 production in PBMCs of healthy individuals (both p. <. 0.001), individuals with past Q fever (p. <. 0.05, p. <. 0.01, respectively) and of patients with chronic Q fever (both p. <. 0.001). SNPs in MMP7 (rs11568810) (p. <. 0.05) and MMP9 (rs17576) (p. <. 0.05) were more common in patients with chronic Q fever. Circulating MMP-7 serum levels were higher in patients with chronic Q fever (median 33.5 ng/mL, interquartile range 22.3-45.7 ng/mL) than controls (20.6 ng/mL, 15.9-33.8 ng/mL). Conclusion: Coxiella burnetii-induced MMP production may contribute to the development of chronic Q fever.
Original languageEnglish
Pages (from-to)487.e7-487.e13
JournalClinical Microbiology and Infection
Volume23
Issue number7
DOIs
Publication statusPublished - 2017

Fingerprint

Q Fever
Matrix Metalloproteinases
Coxiella burnetii
Blood Cells
Single Nucleotide Polymorphism
Matrix Metalloproteinase 7
Infected Aneurysm
Tissue Inhibitor of Metalloproteinases
Matrix Metalloproteinase 1
Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinase 9
Microarray Analysis
Infection
Gram-Negative Bacteria
Genes
Aneurysm
Extracellular Matrix
Lipopolysaccharides
Enzyme-Linked Immunosorbent Assay

Keywords

  • Coxiella burnetii
  • Chronic Q fever
  • Matrix metalloproteinases
  • Pathogenesis
  • Single nucleotide polymorphism
  • Transcriptome analysis

Cite this

Jansen, A. F. M., Schoffelen, T., Textoris, J., Mege, J. L., Bleeker-Rovers, C. P., Roest, H. I. J., ... van Deuren, M. (2017). Involvement of matrix metalloproteinases in chronic Q fever. Clinical Microbiology and Infection, 23(7), 487.e7-487.e13. https://doi.org/10.1016/j.cmi.2017.01.022
Jansen, A.F.M. ; Schoffelen, T. ; Textoris, J. ; Mege, J.L. ; Bleeker-Rovers, C.P. ; Roest, H.I.J. ; Wever, P.C. ; Joosten, L.A.B. ; Netea, M.G. ; van de Vosse, E. ; van Deuren, M. / Involvement of matrix metalloproteinases in chronic Q fever. In: Clinical Microbiology and Infection. 2017 ; Vol. 23, No. 7. pp. 487.e7-487.e13.
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title = "Involvement of matrix metalloproteinases in chronic Q fever",
abstract = "Objectives: Chronic Q fever is a persistent infection with the intracellular Gram-negative bacterium Coxiella burnetii, which can lead to complications of infected aneurysms. Matrix metalloproteinases (MMPs) cleave extracellular matrix and are involved in infections as well as aneurysms. We aimed to study the role of MMPs in the pathogenesis of chronic Q fever. Methods: We investigated gene expression of MMPs through microarray analysis and MMP production with ELISA in C. burnetii-stimulated peripheral blood mononuclear cells (PBMCs) of patients with chronic Q fever and healthy controls. Twenty single nucleotide polymorphisms (SNPs) of MMP and tissue inhibitor of MMP genes were genotyped in 139 patients with chronic Q fever and 220 controls with similar cardiovascular co-morbidity. Additionally, circulating MMPs levels in patients with chronic Q fever were compared with those in cardiovascular controls with and without a history of past Q fever. Results: In healthy controls, the MMP pathway involving four genes (MMP1, MMP7, MMP10, MMP19) was significantly up-regulated in C. burnetii-stimulated but not in Escherichia coli lipopolysaccharide -stimulated PBMCs. Coxiella burnetii induced MMP-1 and MMP-9 production in PBMCs of healthy individuals (both p. <. 0.001), individuals with past Q fever (p. <. 0.05, p. <. 0.01, respectively) and of patients with chronic Q fever (both p. <. 0.001). SNPs in MMP7 (rs11568810) (p. <. 0.05) and MMP9 (rs17576) (p. <. 0.05) were more common in patients with chronic Q fever. Circulating MMP-7 serum levels were higher in patients with chronic Q fever (median 33.5 ng/mL, interquartile range 22.3-45.7 ng/mL) than controls (20.6 ng/mL, 15.9-33.8 ng/mL). Conclusion: Coxiella burnetii-induced MMP production may contribute to the development of chronic Q fever.",
keywords = "Coxiella burnetii, Chronic Q fever, Matrix metalloproteinases, Pathogenesis, Single nucleotide polymorphism, Transcriptome analysis",
author = "A.F.M. Jansen and T. Schoffelen and J. Textoris and J.L. Mege and C.P. Bleeker-Rovers and H.I.J. Roest and P.C. Wever and L.A.B. Joosten and M.G. Netea and {van de Vosse}, E. and {van Deuren}, M.",
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Jansen, AFM, Schoffelen, T, Textoris, J, Mege, JL, Bleeker-Rovers, CP, Roest, HIJ, Wever, PC, Joosten, LAB, Netea, MG, van de Vosse, E & van Deuren, M 2017, 'Involvement of matrix metalloproteinases in chronic Q fever', Clinical Microbiology and Infection, vol. 23, no. 7, pp. 487.e7-487.e13. https://doi.org/10.1016/j.cmi.2017.01.022

Involvement of matrix metalloproteinases in chronic Q fever. / Jansen, A.F.M.; Schoffelen, T.; Textoris, J.; Mege, J.L.; Bleeker-Rovers, C.P.; Roest, H.I.J.; Wever, P.C.; Joosten, L.A.B.; Netea, M.G.; van de Vosse, E.; van Deuren, M.

In: Clinical Microbiology and Infection, Vol. 23, No. 7, 2017, p. 487.e7-487.e13.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Involvement of matrix metalloproteinases in chronic Q fever

AU - Jansen, A.F.M.

AU - Schoffelen, T.

AU - Textoris, J.

AU - Mege, J.L.

AU - Bleeker-Rovers, C.P.

AU - Roest, H.I.J.

AU - Wever, P.C.

AU - Joosten, L.A.B.

AU - Netea, M.G.

AU - van de Vosse, E.

AU - van Deuren, M.

PY - 2017

Y1 - 2017

N2 - Objectives: Chronic Q fever is a persistent infection with the intracellular Gram-negative bacterium Coxiella burnetii, which can lead to complications of infected aneurysms. Matrix metalloproteinases (MMPs) cleave extracellular matrix and are involved in infections as well as aneurysms. We aimed to study the role of MMPs in the pathogenesis of chronic Q fever. Methods: We investigated gene expression of MMPs through microarray analysis and MMP production with ELISA in C. burnetii-stimulated peripheral blood mononuclear cells (PBMCs) of patients with chronic Q fever and healthy controls. Twenty single nucleotide polymorphisms (SNPs) of MMP and tissue inhibitor of MMP genes were genotyped in 139 patients with chronic Q fever and 220 controls with similar cardiovascular co-morbidity. Additionally, circulating MMPs levels in patients with chronic Q fever were compared with those in cardiovascular controls with and without a history of past Q fever. Results: In healthy controls, the MMP pathway involving four genes (MMP1, MMP7, MMP10, MMP19) was significantly up-regulated in C. burnetii-stimulated but not in Escherichia coli lipopolysaccharide -stimulated PBMCs. Coxiella burnetii induced MMP-1 and MMP-9 production in PBMCs of healthy individuals (both p. <. 0.001), individuals with past Q fever (p. <. 0.05, p. <. 0.01, respectively) and of patients with chronic Q fever (both p. <. 0.001). SNPs in MMP7 (rs11568810) (p. <. 0.05) and MMP9 (rs17576) (p. <. 0.05) were more common in patients with chronic Q fever. Circulating MMP-7 serum levels were higher in patients with chronic Q fever (median 33.5 ng/mL, interquartile range 22.3-45.7 ng/mL) than controls (20.6 ng/mL, 15.9-33.8 ng/mL). Conclusion: Coxiella burnetii-induced MMP production may contribute to the development of chronic Q fever.

AB - Objectives: Chronic Q fever is a persistent infection with the intracellular Gram-negative bacterium Coxiella burnetii, which can lead to complications of infected aneurysms. Matrix metalloproteinases (MMPs) cleave extracellular matrix and are involved in infections as well as aneurysms. We aimed to study the role of MMPs in the pathogenesis of chronic Q fever. Methods: We investigated gene expression of MMPs through microarray analysis and MMP production with ELISA in C. burnetii-stimulated peripheral blood mononuclear cells (PBMCs) of patients with chronic Q fever and healthy controls. Twenty single nucleotide polymorphisms (SNPs) of MMP and tissue inhibitor of MMP genes were genotyped in 139 patients with chronic Q fever and 220 controls with similar cardiovascular co-morbidity. Additionally, circulating MMPs levels in patients with chronic Q fever were compared with those in cardiovascular controls with and without a history of past Q fever. Results: In healthy controls, the MMP pathway involving four genes (MMP1, MMP7, MMP10, MMP19) was significantly up-regulated in C. burnetii-stimulated but not in Escherichia coli lipopolysaccharide -stimulated PBMCs. Coxiella burnetii induced MMP-1 and MMP-9 production in PBMCs of healthy individuals (both p. <. 0.001), individuals with past Q fever (p. <. 0.05, p. <. 0.01, respectively) and of patients with chronic Q fever (both p. <. 0.001). SNPs in MMP7 (rs11568810) (p. <. 0.05) and MMP9 (rs17576) (p. <. 0.05) were more common in patients with chronic Q fever. Circulating MMP-7 serum levels were higher in patients with chronic Q fever (median 33.5 ng/mL, interquartile range 22.3-45.7 ng/mL) than controls (20.6 ng/mL, 15.9-33.8 ng/mL). Conclusion: Coxiella burnetii-induced MMP production may contribute to the development of chronic Q fever.

KW - Coxiella burnetii

KW - Chronic Q fever

KW - Matrix metalloproteinases

KW - Pathogenesis

KW - Single nucleotide polymorphism

KW - Transcriptome analysis

U2 - 10.1016/j.cmi.2017.01.022

DO - 10.1016/j.cmi.2017.01.022

M3 - Article

VL - 23

SP - 487.e7-487.e13

JO - Clinical Microbiology and Infection

JF - Clinical Microbiology and Infection

SN - 1198-743X

IS - 7

ER -

Jansen AFM, Schoffelen T, Textoris J, Mege JL, Bleeker-Rovers CP, Roest HIJ et al. Involvement of matrix metalloproteinases in chronic Q fever. Clinical Microbiology and Infection. 2017;23(7):487.e7-487.e13. https://doi.org/10.1016/j.cmi.2017.01.022