Involvement of matrix metalloproteinases in chronic Q fever.
OBJECTIVE
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).


CONCLUSIONS
Coxiella burnetii-induced MMP production may contribute to the development of chronic Q fever.
Department of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands; Radboud Expert Centre for Q fever and Radboud Centre for Infectious Diseases (RCI), Radboud University Medical Centre, The Netherlands. Electronic address: Anne.FM.Jansen@radboudumc.nl.
A F M
AFM
Jansen
Department of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands; Radboud Expert Centre for Q fever and Radboud Centre for Infectious Diseases (RCI), Radboud University Medical Centre, The Netherlands.
T
T
Schoffelen
Université Claude Bernard Lyon 1, Hospices Civils de Lyon, bioMérieux; "Pathophysiology of Injury Induced Immunosuppression (PI3)", Hôpital E. Herriot, Lyon, France.
J
J
Textoris
URMITE, Aix-Marseille University, Marseille, France.
J L
JL
Mege
Department of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands; Radboud Expert Centre for Q fever and Radboud Centre for Infectious Diseases (RCI), Radboud University Medical Centre, The Netherlands.
C P
CP
Bleeker-Rovers
Department of Bacteriology and Epidemiology, Wageningen Bioveterinary Research, Lelystad, The Netherlands.
H I J
HIJ
Roest
Department of Medical Microbiology and Infection Control, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands.
P C
PC
Wever
Department of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands; Radboud Expert Centre for Q fever and Radboud Centre for Infectious Diseases (RCI), Radboud University Medical Centre, The Netherlands.
L A B
LAB
Joosten
Department of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands; Radboud Expert Centre for Q fever and Radboud Centre for Infectious Diseases (RCI), Radboud University Medical Centre, The Netherlands.
M G
MG
Netea
Department of Infectious Diseases, Leiden University Medical Centre, Leiden, The Netherlands.
E
E
van de Vosse
Department of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands; Radboud Expert Centre for Q fever and Radboud Centre for Infectious Diseases (RCI), Radboud University Medical Centre, The Netherlands.
M
M
van Deuren
D016997:Coxiella burnetii / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D005838:Genotype; D054884:Host-Pathogen Interactions; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D020782:Matrix Metalloproteinases / Q000032:analysis* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011778:Q Fever / Q000473:pathology* / Q000503:physiopathology*
D020782:Matrix Metalloproteinases
Chronic Q fever; Coxiella burnetii; Matrix metalloproteinases; Pathogenesis; Single nucleotide polymorphism; Transcriptome analysis