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Infection and Immunity, August 2009, p. 3442-3449, Vol. 77, No. 8
0019-9567/09/$08.00+0 doi:10.1128/IAI.00389-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Chlamydial and Periodontal Pathogens Induce Hepatic Inflammation and Fatty Acid Imbalance in Apolipoprotein E-Deficient Mice
Kati Hyvärinen,1,
*
Anita M. Tuomainen,1,
Saara Laitinen,6
Igor L. Bykov,2
Liisa Törmäkangas,2
Kai Lindros,2
Reijo Käkelä,7
Georg Alfthan,2
Irma Salminen,2
Matti Jauhiainen,2,8
Petri T. Kovanen,3
Maija Leinonen,4
Pekka Saikku,5 and
Pirkko J. Pussinen1
Institute of Dentistry, University of Helsinki, and Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland,1 National Institute for Health and Welfare, Helsinki, Finland,2 Wihuri Research Institute, Helsinki, Finland,3 National Institute for Health and Welfare, Oulu, Finland,4 Department of Medical Microbiology, University of Oulu, Oulu, Finland,5 Finnish Red Cross Blood Service, Helsinki, Finland,6 Institute of Biomedicine, Department of Medical Biochemistry and Developmental Biology, University of Helsinki, Helsinki, Finland,7 FIMM, Institute for Molecular Medicine, Helsinki, Finland8
Received 7 April 2009/ Returned for modification 6 May 2009/ Accepted 11 May 2009
Periodontitis and Chlamydia pneumoniae infection are independent risk factors for cardiovascular diseases. The aim of this study was to investigate the effect of C. pneumoniae and Aggregatibacter actinomycetemcomitans infection on hepatic inflammation and lipid homeostasis of apolipoprotein E-deficient mice. Mice were infected with viable C. pneumoniae intranasally three times for chronic infection or once for acute infection. Viable A. actinomycetemcomitans was administered 10 times intravenously alone or in concert with C. pneumoniae. Hepatic alterations were assessed by histochemistry, lipid quantification, and fatty acid profile analysis. The RNA expression levels and the presence of pathogens in the livers and lungs were detected by quantitative real-time PCR. Both pathogens were detected in the livers of the infected animals. Chronic C. pneumoniae infection induced marked changes in hepatic lipid homeostasis. A. actinomycetemcomitans infection resulted in inflammatory cell infiltration into the liver, accompanied by elevated hepatic RNA expression levels of inflammation-related genes and higher serum amyloid A and lipopolysaccharide concentrations. Our results indicate that proatherogenic pathogens infect the liver, causing proinflammatory alterations and lipid disturbances. This infection may maintain chronic systemic inflammation attributable to atherogenesis.
* Corresponding author. Mailing address: Institute of Dentistry, P.O. Box 63, Biomedicum, Haartmaninkatu 8, 00014 University of Helsinki, Helsinki, Finland. Phone: 358 9 191 25570. Fax: 358 9 191 25194. E-mail: kati.hyvarinen{at}helsinki.fi
Published ahead of print on 18 May 2009.
These authors contributed equally to this work.
Infection and Immunity, August 2009, p. 3442-3449, Vol. 77, No. 8
0019-9567/09/$08.00+0 doi:10.1128/IAI.00389-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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