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Detection of Chlamydophila pneumoniae in dendritic cells in atherosclerotic lesions

  • Yuri V Bobryshev
    Correspondence
    Corresponding author. Tel.: +61-2-8382-2395; fax: +61-2-9360-4424.
    Affiliations
    Surgical Professorial Unit, St. Vincent’s Hospital, University of New South Wales, Sydney, NSW 2010, Australia

    National University Medical Institutes, National University of Singapore, Singapore 117597, Singapore
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  • Weiping Cao
    Affiliations
    National University Medical Institutes, National University of Singapore, Singapore 117597, Singapore
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  • Meng Chee Phoon
    Affiliations
    Programme in Infectious Diseases, Department of Microbiology, Faculty of Medicine, National University of Singapore, Singapore 117597, Singapore
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  • Dinh Tran
    Affiliations
    Surgical Professorial Unit, St. Vincent’s Hospital, University of New South Wales, Sydney, NSW 2010, Australia

    Division of Anatomical Pathology, St. Vincent’s Hospital, Sydney, NSW 2010, Australia
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  • Vincent T.K Chow
    Affiliations
    Programme in Infectious Diseases, Department of Microbiology, Faculty of Medicine, National University of Singapore, Singapore 117597, Singapore
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  • Reginald S.A Lord
    Affiliations
    National University Medical Institutes, National University of Singapore, Singapore 117597, Singapore
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  • Jinhua Lu
    Affiliations
    National University Medical Institutes, National University of Singapore, Singapore 117597, Singapore

    Programme in Infectious Diseases, Department of Microbiology, Faculty of Medicine, National University of Singapore, Singapore 117597, Singapore
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      Abstract

      Dendritic cells (DCs) populate atherosclerotic lesions and might be involved in the regulation of immune reactions in atherosclerosis. The present work was undertaken to examine a possible association of DCs with Chlamydophila pneumoniae in human atherosclerotic plaques obtained by endarterectomy. C. pneumoniae was identified in 17 of 60 (28%) atherosclerotic plaques by a combination of immunohistochemistry and polymerase chain reaction (PCR). Double immunohistochemistry identified the presence of C. pneumoniae within S100+ DCs that were localised predominantly in the deep layer of the intima under the necrotic core. Quantitative analysis showed that there were no differences in the numbers of DCs between C. pneumoniae+ and C. pneumoniae groups of atherosclerotic specimens. There were also no differences in the expression of Lag-antigen and HLA-DR by DCs between the groups of specimens. Markers of DC activation CD80 and CD86 were absent from both groups of specimens. Flow cytometry analysis of the effects of C. pneumoniae infection on immature monocyte-derived DCs in vitro showed no changes in the expression of CD1a, MHC class II, CD80 and CD86. The results of this study demonstrate that C. pneumoniae might infect DCs within the atherosclerotic intima but whether the presence of C. pneumoniae in DCs affects the intensity of immune reactions in atherosclerosis needs further clarification.

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      References

        • Hansson G.K
        Immune mechanisms in atherosclerosis.
        Arterioscler. Thromb. Vasc. Biol. 2001; 21: 1876-1890
        • Hansson G.K
        • Libby P
        • Schonbeck U
        • Yan Z.Q
        Innate and adaptive immunity in the pathogenesis of atherosclerosis.
        Circ. Res. 2002; 91: 281-291
        • de Boer O.J
        • van der Wal A.C
        • Becker A.E
        Atherosclerosis, inflammation, and infection.
        J. Pathol. 2000; 190: 237-243
        • Biocina B
        • Husedzinovic I
        • Sutlic Z
        • Presecki V
        • Wallwork J
        Cytomegalovirus disease as a possible etiologic factor for early atherosclerosis.
        Coll. Antropol. 1999; 23: 673-681
        • Kusters J.G
        • Kuipers E.J
        Helicobacter and atherosclerosis.
        Am. Heart J. 1999; 138: S523-S527
        • Campbell L.A
        • Kuo C.C
        Chlamydia pneumoniae and atherosclerosis.
        Semin. Respir. Infect. 2003; 18: 48-54
        • Kalayoglu M.V
        • Libby P
        • Byrne G.I
        Chlamydia pneumoniae as an emerging risk factor in cardiovascular disease.
        JAMA. 2002; 288: 2724-2731
        • Hammerschlag M.R
        The intracellular life of chlamydiae.
        Semin. Pediatr. Infect. Dis. 2002; 13: 239-248
        • Campbell L.A
        • Kuo C.C
        ChLamydia pneumoniae pathogenesis.
        J. Med. Microbiol. 2002; 51: 623-625
        • Koh W.P
        • Taylor M.B
        • Hughes K
        • Chew S.K
        • Fong C.W
        • Phoon M.C
        • et al.
        Seroprevalence of IgG antibodies against Chlamydia pneumoniae in Chinese.
        Int. J. Epidemiol. 2002; 31: 1001-1007
        • Saikku P
        • Leinonen M
        • Mattila K
        • Ekman M.R
        • Nieminen M.S
        • Makela P.H
        • et al.
        Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction.
        Lancet. 1988; 2: 983-986
        • Weiss S.M
        • Roblin P.M
        • Gaydos C.A
        • et al.
        Failure to detect Chlamydia pneumoniae in coronary atheromas of patients undergoing atherectomy.
        J. Infect. Dis. 1996; 173: 957-962
        • Paterson D.L
        • Hall J
        • Rasmussen S.J
        • Timms P
        Failure to detect Chlamydia pneumoniae in atherosclerotic plaques of Australian patients.
        Pathology. 1998; 30: 169-172
        • Ong G.M
        • Coyle P.V
        • Barros D’Sa A.A
        • et al.
        Non-detection of Chlamydia species in carotid atheroma using generic primers by nested PCR in a population with a high prevalence of Chlamydia pneumoniae antibody.
        BMC Infect. Dis. 2001; 1: 12
        • Johnson W.D
        • Moses J
        • Kipshidze N
        Absence of Chlamydia pneumoniae in surgical specimens of coronary and carotid arteries by polymerase chain reaction.
        Cardiovasc. Radiat. Med. 2001; 2: 221-224
        • Bishara J
        • Pitlik S
        • Kazakov A
        • et al.
        Failure to detect Chlamydia pneumoniae by cell culture and polymerase chain reaction in major arteries of 93 patients with atherosclerosis.
        Eur. J. Clin. Microbiol. Infect. Dis. 2003; 22: 300-302
        • Kuo C.C
        • Gown A.M
        • Benditt E.P
        • Grayston J.T
        Detection of Chlamydia pneumoniae in aortic lesions of atherosclerosis by immunocytochemical stain.
        Arterioscler. Thromb. 1993; 13: 1501-1504
        • Kuo C.C
        • Shor A
        • Campbell L.A
        • Fukushi H
        • Patton D.L
        • Grayston J.T.R
        Demonstration of Chlamydia pneumoniae in atherosclerotic lesions of coronary arteries.
        J. Infect. Dis. 1993; 167: 841-849
        • Jackson L.A
        • Campbell L.A
        • Kuo C.C
        • Rodriguez D.I
        • Lee A
        • Grayston J.T
        Isolation of Chlamydia pneumoniae from a carotid endarterectomy specimen.
        J. Infect. Dis. 1997; 176: 292-295
        • Yamashita K
        • Ouchi K
        • Shirai M
        • Gondo T
        • Nakazawa T
        • Ito H
        Distribution of Chlamydia pneumoniae infection in the athersclerotic carotid artery.
        Stroke. 1998; 29: 773-778
        • Prager M
        • Turel Z
        • Speidl W.S
        • et al.
        Chlamydia pneumoniae in carotid artery atherosclerosis: a comparison of its presence in atherosclerotic plaque, healthy vessels, and circulating leukocytes from the same individuals.
        Stroke. 2002; 33: 2756-2761
        • Hortovanyi E
        • Illyes G
        • Glasz T
        • Kadar A
        Chlamydia pneumoniae in different coronary artery segments in the young.
        Pathol. Res. Pract. 2002; 198: 19-23
        • Neureiter D
        • Heuschmann P
        • Stintzing S
        • et al.
        Detection of Chlamydia pneumoniae but not of Helicobacter pylori in symptomatic atherosclerotic carotids associated with enhanced serum antibodies.
        Atherosclerosis. 2003; 168: 153-162
        • Vink A
        • Poppen M
        • Schoneveld A.H
        • et al.
        Distribution of Chlamydia pneumoniae in the human arterial system and its relation to the local amount of atherosclerosis within the individual.
        Circulation. 2001; 103: 1613-1617
        • Rassu M
        • Cazzavillan S
        • Scagnelli M
        • et al.
        Demonstration of Chlamydia pneumoniae in atherosclerotic arteries from various vascular regions.
        Atherosclerosis. 2001; 158: 73-79
        • Loehe F
        • Bittmann I
        • Weilbach C
        • Lauterjung L
        • Schildberg F.W
        • Heiss M.M
        Chlamydia pneumoniae in atherosclerotic lesions of patients undergoing vascular surgery.
        Ann. Vasc. Surg. 2002; 16: 467-473
      1. Koh WP, Taylor MB, Chew SK, Phoon MC, Kang KL, Chow VT. Chlamydia pneumoniae IgG seropositivity and clinical history of ischemic heart disease in Singapore. J Microbiol Immunol Infect 2003, 36:169–74.

        • Bobryshev Y.V
        • Lord R.S.A
        Ultastructural recognition of cells with dendritic cell morphology in human aortic intima. Contacting interactions of vascular dendritic cells in athero-resistant and athero-prone areas of the aorta.
        Arch. Histol. Cytol. 1995; 58: 307-322
        • Bobryshev Y.V
        • Lord R.S.A
        Mapping of vascular dendritic cells in atherosclerotic arteries suggests their involvement in local immune-inflammatory reactions.
        Cardiovasc. Res. 1998; 37: 799-810
        • Bobryshev Y.V
        Dendritic cells and their involvement in atherosclerosis.
        Curr. Opin. Lipidol. 2000; 11: 511-517
        • Steinman R.M
        • Cohn Z.A
        Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution.
        J. Exp. Med. 1973; 137: 1142-1162
        • Banchereau J
        • Steinman R.M
        Dendritic cells and control of immunity.
        Nature. 1998; 392: 245-252
      2. Lotze MT, Thomson AW, editors. Dendritic cells: biology and clinical applications. 2nd ed. San Diego: Academic Press, 2001.

      3. World Medical Association Declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. Cardiovasc Res 1997;35:2–3.

        • Bobryshev Y.V
        • Lord R.S.A
        S100 positive cells in human arterial intima and in atherosclerotic lesions.
        Cardiovasc. Res. 1995; 29: 689-696
        • Kashihara M
        • Ueda M
        • Horiguchi Y
        • Furukawa F
        • Hanaoka M
        • Imamura S
        A monoclonal antibody specifically reactive to human Langerhans cells.
        J. Invest. Dermatol. 1986; 87: 602-607
        • Bobryshev Y.V
        • Ikezawa T
        • Watanabe T
        Formation of Birbeck granule-like structures in vascular dendritic cells in human atherosclerotic aorta. Lag-antibody to epidermal Langerhans cells recognizes cells in the aortic wall.
        Atherosclerosis. 1997; 133: 193-202
        • Valladeau J
        • Ravel O
        • Dezutter-Dambuyant C
        • et al.
        Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules.
        Immunity. 2000; 12: 71-81
        • Furness G
        • Graham D.M
        • Reeve R
        The titration of trachoma and inclusion blenorhoea virus in cell culture.
        J. Gen. Microbiol. 1960; 23: 613-619
        • Campbell L.A
        • Perez Melgosa M
        • Hamilton D.J
        • Kuo C.C
        • Grayston J.T
        Detection of Chlamydia pneumoniae by polymerase chain reaction.
        J. Clin. Microbiol. 1992; 30: 434-439
        • Cao W
        • Bobryshev Y.V
        • Lord R.S.A
        • Reida E.I.O
        • Lee S.H
        • Lu J
        Dendritic cells in the arterial wall express C1q: potential significance in atherogenesis.
        Cardiovasc. Res. 2003; 60: 175-186
        • Chow V.T.K
        • Phoon M.C
        Seroepidemiological survey of Chlamydia pneumoniae infection among Singapore university undergraduates: comparison between microimmunofluorescence and neutralization tests.
        World J. Microbiol. Biotechnol. 2001; 17: 773-778
        • Stary H.C
        • Chandler A.B
        • Dinsmore R.E
        • Fuster V
        • Glagov S
        • Insull Jr., W
        • et al.
        A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association.
        Circulation. 1995; 92: 1355-1374
        • Haranaga S
        • Yamaguchi H
        • Leparc G.F
        • Friedman H
        • Yamamoto Y
        Detection of Chlamydia pneumoniae antigenin PBMNCs of healthy blood donors.
        Transfusion. 2001; 41: 1114-1119
        • Tsirpanlis G
        • Chatzipanagiotou S
        • Ioannidis A
        • Moutafis S
        • Poulopoulou C
        • Nicolaou C
        Detection of Chlamydia pneumoniae in peripheral blood mononuclear cells: correlation with inflammation and atherosclerosis in haemodialysis patients.
        Nephrol. Dial. Transplant. 2003; 18: 918-923
        • Gieffers J
        • Fullgraf H
        • Jahn J
        • et al.
        Chlamydia pneumoniae infection in circulating human monocytes is refractory to antibiotic treatment.
        Circulation. 2001; 23: 351-356
        • Muller J
        • Nyvad O
        • Larsen N.A
        • Lokkegaard N
        • Pedersen R.S
        • Solling J
        • et al.
        Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in dialysis patients.
        Scand. J. Clin. Lab. Invest. 2002; 62: 503-509
        • Kalayoglu M.V
        • Perkins B.N
        • Byrne G.I
        Chlamydia pneumoniae-infected monocytes exhibit increased adherence to human aortic endothelial cells.
        Microbes Infect. 2001; 3: 963-969
        • Randolph G.J
        • Beaulieu S
        • Lebecque S
        • Steinman R.M
        • Muller W.A
        Differentiation of monocytes into dendritic cells in a model of transendothelial trafficking.
        Science. 1998; 282: 480-483
        • Bobryshev Y.V
        • Lord R.S
        Structural heterogeneity and contacting interactions of vascular dendritic cells in early atherosclerotic lesions of the human aorta.
        J. Submicrosc. Cytol. Pathol. 1996; 28: 49-60
        • Apfalter P
        • Assadian O
        • Blasi F
        • et al.
        Reliability of nested PCR for detection of Chlamydia pneumoniae DNA in atheromas: results from a multicenter study applying standardized protocols.
        J. Clin. Microbiol. 2002; 40: 4428-4434
        • Cochrane M
        • Pospischil A
        • Walker P
        • Gibbs H
        • Timms P
        Distribution of Chlamydia pneumoniae DNA in atherosclerotic carotid arteries: significance for sampling procedures.
        J. Clin. Microbiol. 2003; 41: 1454-1457
        • Dowell S.F
        • Peeling R.W
        • Boman J
        • et al.
        Standardizing Chlamydia pneumoniae assays: recommendations from the Centers for Disease Control and Prevention (USA) and the Laboratory Centre for Disease Control (Canada).
        Clin. Infect. Dis. 2001; 33: 492-503
        • Vammen S
        • Vorum H
        • Ostergaard L
        • Henneberg E.W
        • Lindholt J.S
        Immunoblotting analysis of abdominal aortic aneurysms using antibodies against Chlamydia pneumoniae recombinant MOMP.
        Eur. J. Vasc. Endovasc. Surg. 2002; 24: 81-85
        • Prebeck S
        • Kirschning C
        • Durr S
        • da Costa C
        • et al.
        Predominant role of toll-like receptor 2 versus 4 in Chlamydia pneumoniae-induced activation of dendritic cells.
        J. Immunol. 2001; 15: 3316-3323
        • Netea M.G
        • Kullberg B.J
        • Galama J.M
        • Stalenhoef A.F
        • Dinarello C.A
        • van der Meer J.W
        Non-LPS components of Chlamydia pneumoniae stimulate cytokine production through Toll-like receptor 2-dependent pathways.
        Eur. J. Immunol. 2002; 32: 1188-1195
        • Costa C.P
        • Kirschning C.J
        • Busch D
        • et al.
        Role of chlamydial heat shock protein 60 in the stimulation of innate immune cells by Chlamydia pneumoniae.
        Eur. J. Immunol. 2002; 32: 2460-2470
        • Haranaga S
        • Yamaguchi H
        • Friedman H
        • Izumi S
        • Yamamoto Y
        Chlamydia pneumoniae infects and multiplies in lymphocytes in vitro.
        Infect. Immun. 2001; 69: 7753-7759
        • de Boer O.J
        • van der Wal A.C
        • Houtkamp M.A
        • Ossewaarde J.M
        • Teeling P
        • Becker A.E
        Unstable atherosclerotic plaques contain T-cells that respond to Chlamydia pneumoniae.
        Cardiovasc. Res. 2000; 48: 402-408
        • Kaul R
        • Uphoff J
        • Wiedeman J
        • Yadlapalli S
        • Wenman W.M
        Detection of Chlamydia pneumoniae DNA in CD3+ lymphocytes from healthy blood donors and patients with coronary artery disease.
        Circulation. 2000; 102: 2341-2346
        • van der Wal A.C
        Chlamydia pneumoniae inside the atherosclerotic plaque—does it affect plaque inflammation and plaque progression.
        Cardiovasc. Res. 2002; 56: 178-180
        • Kalayoglu M.V
        • Byrne G.I
        Induction of macrophage foam cell formation by Chlamydia pneumoniae.
        J. Infect. Dis. 1998; 177: 725-729