Chlamydophila pneumoniae

Matthias Krüll; Matthias Maass; Norbert Suttorp; Jan Rupp

doi:10.1160/TH05-04-0261

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 94(02): 319-326
DOI: 10.1160/TH05-04-0261

Theme Issue Article

Schattauer GmbH

Chlamydophila pneumoniae

Mechanisms of target cell infection and activation

Matthias Krüll

¹Department. of Internal Medicine/Infectious Diseases, Charité, Universitätsmedizin Berlin, Berlin, Germany

,

Matthias Maass

²SALK Labor, Salzburger Landeskliniken, Salzburg, Austria

,

Norbert Suttorp

¹Department. of Internal Medicine/Infectious Diseases, Charité, Universitätsmedizin Berlin, Berlin, Germany

,

Jan Rupp

³Institute of Medical Microbiology and Hygiene, University of Lübeck, Lübeck, Germany

› Author Affiliations

Abstract

Summary

Chlamydophila (Chlamydia) pneumoniae, a gram-negative obligate intracellular bacterium, is a widespread respiratory pathogen. Chronic C. pneumoniae infection has been suggested as a trigger/ promoter of inflammation that may result in vascular lesions. Although the genome of C. pneumoniae has been sequenced completely this information has not yet led to an understanding of the mechanisms of acute infection and target cell activation nor to the identification of potential chlamydial virulence factors. Intriguingly, current antibiotic treatment options for acute chlamy- dial infection were proven to be ineffective with respect to clinical outcome in different groups of atherosclerotic patients. The reason might be that primary infection of vascular smooth muscle cells and blood monocytes with C. pneumoniae resembles rather a persistent, antibiotic-resistant, than an active infection. In this review we will focus on the importance of putative host cell receptors for C.pneumoniae and subsequently activated signal transduction pathways.

Keywords

Atherosclerosis - endothelial cells - infection / bacterial - viral - signal transduction - bacteria

Full Text

References

References
1 Cook PJ, Davies P, Tunnicliffe W. et al. Chlamydia pneumoniae and asthma. Thorax 1998; 53: 254-59.
2 Grayston JT, Campbell LA, Kuo CC. et al. A new respiratory tract pathogen: Chlamydia pneumoniae strain TWAR. J Infect Dis 1990; 161: 618-25.
3 Wu L, Skinner SJ, Lambie N. et al. Immunohistochemical staining for Chlamydia pneumoniae is increased in lung tissue from subjects with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000; 162: 1148-51.
4 Grayston JT, Aldous MB, Easton A. et al. Evidence that Chlamydia pneumoniae causes pneumonia and bronchitis. J Infect Dis 1993; 168: 1231-5.
5 Saikku P, Leinonen M, Tenkanen L. et al. Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki Heart Study. Ann Intern Med 1992; 116: 273-8.
6 Thom DH, Grayston JT, Siscovick DS. et al. Association of prior infection with Chlamydia pneumoniae and angiographically demonstrated coronary artery disease. JAMA 1992; 268: 68-72.
7 Kuo CC, Shor A, Campbell LA. et al. Demonstration of Chlamydia pneumoniae in atherosclerotic lesions of coronary arteries. J Infect Dis 1993; 167: 841-9.
8 Maass M, Bartels C, Engel PM. et al. Endovascular presence of viable Chlamydia pneumoniae is a common phenomenon in coronary artery disease. J Am Coll Cardiol 1998; 31: 827-32.
9 Ngeh J, Anand V, Gupta S. Chlamydia pneumoniae and atherosclerosis – what we know and what we don’t. Clin Microbiol Infect 2002; 8: 2-13.
10 Elkind MS, Lin IF, Grayston JT. et al. Chlamydia pneumoniae and the risk of first ischemic stroke : The Northern Manhattan Stroke Study. Stroke 2000; 31: 1521-5.
11 Saikku P, Leinonen M, Mattila K. et al. Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet 1988; 2: 983-6.
12 Sander D, Winbeck K, Klingelhofer J. et al. Enhanced progression of early carotid atherosclerosis is related to Chlamydia pneumoniae (Taiwan acute respiratory) seropositivity. Circulation 2001; 103: 1390-5.
13 Muhlestein JB. Antibiotic treatment of atherosclerosis. Curr Opin Lipidol 2003; 14: 605-14.
14 Shor A, Kuo CC, Patton DL. Detection of Chlamydia pneumoniae in coronary arterial fatty streaks and atheromatous plaques. S Afr Med J 1992; 82: 158-61.
15 Campbell LA, O’Brien ER, Cappuccio AL. et al. Detection of Chlamydia pneumoniae TWAR in human coronary atherectomy tissues. J Infect Dis 1995; 172: 585-8.
16 Taylor-Robinson D, Thomas BJ. Chlamydia pneumoniae in atherosclerotic tissue. J Infect Dis 2000; 181 (Suppl. 03) S437-S40.
17 Ramirez JA. Isolation of Chlamydia pneumoniae from the coronary artery of a patient with coronary atherosclerosis. The Chlamydia pneumoniae/Atherosclerosis Study Group. Ann Intern Med 1996; 125: 979-82.
18 Moazed TC, Kuo C, Grayston JT. et al. Murine models of Chlamydia pneumoniae infection and atherosclerosis. J Infect Dis 1997; 175: 883-90.
19 Muhlestein JB, Anderson JL, Hammond EH. et al. Infection with Chlamydia pneumoniae accelerates the development of atherosclerosis and treatment with azithromycin prevents it in a rabbit model. Circulation 1998; 97: 633-6.
20 Fong IW, Chiu B, Viira E. et al. De novo induction of atherosclerosis by Chlamydia pneumoniae in a rabbit model. Infect Immun 1999; 67: 6048-55.
21 Blessing E, Campbell LA, Rosenfeld ME. et al. Chlamydia pneumoniae infection accelerates hyperlipidemia induced atherosclerotic lesion development in C57BL/6J mice. Atherosclerosis 2001; 158: 13-17.
22 Fong IW, Chiu B, Viira E. etal. Influence of clarithromycin on early atherosclerotic lesions after Chlamydia pneumoniae infection in a rabbit model. Antimicrob Agents Chemother 2002; 46: 2321-6.
23 Gieffers J, van Zandbergen G, Rupp J. et al. Phagocytes transmit Chlamydia pneumoniae from the lungs to the vasculature. Eur Respir J 2004; 23: 506-10.
24 Gurfinkel E, Bozovich G, Daroca A. et al. Randomised trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS Pilot Study. ROXIS Study Group. Lancet 1997; 350: 404-7.
25 Gurfinkel E. Inflammation, infection, or both in atherosclerosis: the ROXIS trial in perspective. J Infect Dis 2000; 181 (Suppl. 03) S566-S568.
26 Muhlestein JB. Antibiotic treatment of atherosclerosis. Curr Opin Lipidol 2003; 14: 605-14.
27 O’Connor CM, Dunne MW, Pfeffer MA. et al. Azithromycin for the secondary prevention of coronary heart disease events: the WIZARD study: a randomized controlled trial. JAMA 2003; 290: 1459-66.
28 Cercek B, Shah PK, Noc M. et al. Effect of shortterm treatment with azithromycin on recurrent ischaemic events in patients with acute coronary syndrome in the Azithromycin in Acute Coronary Syndrome (AZACS) trial: a randomised controlled trial. Lancet 2003; 361: 809-13.
29 Grayston JT. Antibiotic treatment of atherosclerotic cardiovascular disease. Circulation 2003; 107: 1228-30.
30 Gelfand EV, Cannon CP. Antibiotics for secondary prevention of coronary artery disease: an ACES hypothesis but we need to PROVE IT. Am Heart J 2004; 147: 202-9.
31 Beatty WL, Morrison RP, Byrne GI. Persistent chlamydiae: from cell culture to a paradigm for chlamydial pathogenesis. Microbiol Rev 1994; 58: 686-99.
32 Malinverni R, Kuo CC, Campbell LA. et al. Effects of two antibiotic regimens on course and persistence of experimental Chlamydia pneumoniae TWAR pneumonitis. Antimicrob Agents Chemother 1995; 39: 45-9.
33 Gieffers J, Fullgraf H, Jahn J. et al. Chlamydia pneumoniae infection in circulating human monocytes is refractory to antibiotic treatment. Circulation 2001; 103: 351-6.
34 Ross R. Atherosclerosis–an inflammatory disease. N Engl J Med 1999; 340: 115-26.
35 Gaydos CA, Summersgill JT, Sahney NN. et al. Replication of Chlamydia pneumoniae in vitro in human macrophages, endothelial cells, and aortic artery smooth muscle cells. Infect Immun 1996; 64: 1614-20.
36 Kaukoranta-Tolvanen SS, Laitinen K, Saikku P. et al. Chlamydia pneumoniae multiplies in human endothelial cells in vitro. Microb Pathog 1994; 16: 313-9.
37 Kaukoranta-Tolvanen SS, Teppo AM, Laitinen K. et al. Growth of Chlamydia pneumoniae in cultured human peripheral blood mononuclear cells and induction of a cytokine response. Microb Pathog 1996; 21: 215-21.
38 Godzik KL, O’Brien ER, Wang SK. et al. In vitro susceptibility of human vascular wall cells to infection with Chlamydia pneumoniae . J Clin Microbiol 1995; 33: 2411-4.
39 Moazed TC, Kuo CC, Grayston JT. et al. Evidence of systemic dissemination of Chlamydia pneumoniae via macrophages in the mouse. J Infect Dis 1998; 177: 1322-5.
40 Quinn TC, Gaydos CA. In vitro infection and pathogenesis of Chlamydia pneumoniae in endovascular cells. Am Heart J 1999; 138: S507-S511.
41 Hackstadt T, Fischer ER, Scidmore MA. et al. Origins and functions of the chlamydial inclusion. Trends Microbiol 1997; 5: 288-93.
42 Coombes BK, Mahony JB. Identification of MEKand phosphoinositide 3-kinase-dependent signalling as essential events during Chlamydia pneumoniae invasion of HEp2 cells. Cell Microbiol 2002; 4: 447-60.
43 Roblin PM, Dumornay W, Hammerschlag MR. Use of HEp-2 cells for improved isolation and passage of Chlamydia pneumoniae . J Clin Microbiol 1992; 30: 1968-71.
44 Wong KH, Skelton SK, Chan YK. Efficient culture of Chlamydia pneumoniae with cell lines derived from the human respiratory tract. J Clin Microbiol 1992; 30: 1625-30.
45 Moulder JW. Interaction of chlamydiae and host cells in vitro. Microbiol Rev 1991; 55: 143-90.
46 Ward ME, Murray A. Control mechanisms governing the infectivity of Chlamydia trachomatis for HeLa cells: mechanisms of endocytosis. J Gen Microbiol 1984; 130: 1765-80.
47 Reynolds DJ, Pearce JH. Characterization of the cytochalasin D-resistant (pinocytic) mechanisms of endocytosis utilized by chlamydiae. Infect Immun 1990; 58: 3208-16.
48 Fudyk T, Olinger L, Stephens RS. Selection of mutant cell lines resistant to infection by Chlamydia trachomatis and Chlamydia pneumoniae . Infect Immun 2002; 70: 6444-7.
49 Byrne GI, Moulder JW. Parasite-specified phagocytosis of Chlamydia psittaci and Chlamydia trachomatis by L and HeLa cells. Infect Immun 1978; 19: 598-606.
50 Vretou E, Goswami PC, Bose SK. Adherence of multiple serovars of Chlamydia trachomatis to a common receptor on HeLa and McCoy cells is mediated by thermolabile protein(s). J Gen Microbiol 1989; 135: 3229-37.
51 Davis CH, Raulston JE, Wyrick PB. Protein disulfide isomerase, a component of the estrogen receptor complex, is associated with Chlamydia trachomatis serovar E attached to human endometrial epithelial cells. Infect Immun 2002; 70: 3413-8.
52 Wuppermann FN, Hegemann JH, Jantos CA. Heparan sulfate-like glycosaminoglycan is a cellular receptor for Chlamydia pneumoniae . J Infect Dis 2001; 184: 181-7.
53 Beswick EJ, Travelstead A, Cooper MD. Comparative studies of glycosaminoglycan involvement in Chlamydia pneumoniae and C. trachomatis invasion of host cells. J Infect Dis 2003; 187: 1291-300.
54 Kalman S, Mitchell W, Marathe R. et al. Comparative genomes of Chlamydia pneumoniae and C. trachomatis. Nat Genet 1999; 21: 385-9.
55 Stephens RS, Koshiyama K, Lewis E. et al. Heparinbinding outer membrane protein of chlamydiae. Mol Microbiol 2001; 40: 691-9.
56 Bulut Y, Faure E, Thomas L. et al. Chlamydial heat shock protein 60 activates macrophages and endothelial cells through Toll-like receptor 4 and MD2 in a MyD88-dependent pathway. J Immunol 2002; 168: 1435-40.
57 Netea MG, Kullberg BJ, Galama JM. et al. Non-LPS components of Chlamydia pneumoniae stimulate cytokine production through Toll-like receptor 2-dependent pathways. Eur J Immunol 2002; 32: 1188-95.
58 Prebeck S, Kirschning C, Durr S. et al. Predominant role of toll-like receptor 2 versus 4 in Chlamydia pneumoniae- induced activation of dendritic cells. J Immunol 2001; 167: 3316-23.
59 Sasu S, La Verda D, Qureshi N. et al. Chlamydia pneumoniae and chlamydial heat shock protein 60 stimulate proliferation of human vascular smooth muscle cells via toll-like receptor 4 and p44/p42 mitogen- activated protein kinase activation. Circ Res 2001; 89: 244-50.
60 Bea F, Puolakkainen MH, McMillen T. et al. Chlamydia pneumoniae induces tissue factor expression in mouse macrophages via activation of Egr-1 and the MEK-ERK1/2 pathway. Circ Res 2003; 92: 394-401.
61 Costa CP, Kirschning CJ, 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: 2460-70.
62 Rothfuchs AG, Trumstedt C, Wigzell H, Rottenberg ME. Intracellular bacterial infection-induced IFNgamma is critically but not solely dependent on Tolllike receptor 4-myeloid differentiation factor 88-IFNalpha beta-STAT1 signaling. J Immunol 2004; 172: 6345-53.
63 Haralambieva IH, Iankov ID, Ivanova PV. et al. Chlamydophila pneumoniae induces p44/p42 mitogenactivated protein kinase activation in human fibroblasts through Toll-like receptor 4. J Med Microbiol 2004; 53 (Pt 12) 1187-93.
64 Netea MG, Kullberg BJ, Jacobs LE. et al. Chlamydia pneumoniae stimulates IFN-gamma synthesis through MyD88-dependent , TLR2– and TLR4-independent induction of IL-18 release. J Immunol 2004; 173: 1477-82.
65 Da Costa CU, Wantia N, Kirschning CJ. et al. Heat shock protein 60 from Chlamydia pneumoniae elicits an unusual set of inflammatory responses via Toll-like receptor 2 and 4 in vivo. Eur J Immunol 2004; 34: 2874-84.
66 Erridge C, Pridmore A, Eley A. et al. Lipopolysaccharides of Bacteroides fragilis, Chlamydia trachomatis and Pseudomonas aeruginosa signal via toll-like receptor. J Med Microbiol 2004; 53 (Pt 8) 735-40.
67 Faure E, Equils O, Sieling PA. et al. Bacterial lipopolysaccharide activates NF-kappaB through toll-like receptor 4 (TLR-4) in cultured human dermal endothelial cells. Differential expression of TLR-4 and TLR-2 in endothelial cells. J Biol Chem 2000; 275: 11058-63.
68 Chamaillard M, Girardin SE, Viala J. et al. Nods, Nalps and Naip: intracellular regulators of bacterial-induced inflammation. Cell Microbiol 2003; 5: 581-92.
69 Inohara N, Nunez G. NODs: intracellular proteins involved in inflammation and apoptosis. Nat Rev Immunol 2003; 3: 371-82.
70 Chamaillard M, Hashimoto M, Horie Y. et al. An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid. Nat Immunol 2003; 4: 702-7.
71 Girardin SE, Boneca IG, Carneiro LA. et al. Nod1 detects a unique muropeptide from gram-negative bacterial peptidoglycan. Science 2003; 300: 1584-7.
72 Girardin SE, Boneca IG, Viala J. et al. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem 2003; 278: 8869-72.
73 Inohara N, Ogura Y, Fontalba A. et al. Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn’s disease. J Biol Chem 2003; 278: 5509-12.
74 Bertin J, Nir WJ, Fischer CM. et al. Human CARD4 protein is a novel CED-4/Apaf-1 cell death family member that activates NF-kappaB. J Biol Chem 1999; 274: 12955-8.
75 Gutierrez O, Pipaon C, Inohara N. et al. Induction of Nod2 in myelomonocytic and intestinal epithelial cells via nuclear factor-kappa B activation. J Biol Chem 2002; 277: 41701-5.
76 Inohara N, Koseki T, del Peso L. et al. Nod1, an Apaf-1-like activator of caspase-9 and nuclear factorkappaB. J Biol Chem 1999; 274: 14560-7.
77 Ogura Y, Inohara N, Benito A. et al. Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB. J Biol Chem 2001; 276: 4812-8.
78 Opitz B, Forster S, Hocke AC. et al. Nod1-mediated endothelial cell activation by Chlamydophila pneumoniae . Circ Res 2005; 96: 319-26.
79 Krull M, Kramp J, Petrov T. et al. Differences in cell activation by Chlamydophila pneumoniae and Chlamydia trachomatis infection in human endothelial cells. Infect Immun 2004; 72: 6615-21.
80 Hesse L, Bostock J, Dementin S. et al. Functional and biochemical analysis of Chlamydia trachomatis MurC, an enzyme displaying UDP-N-acetylmuramate: amino acid ligase activity. J Bacteriol 2003; 185: 6507-12.
81 McCoy AJ, Sandlin RC, Maurelli AT. In vitro and in vivo functional activity of Chlamydia MurA, a UDPN N- acetylglucosamine enolpyruvyl transferase involved in peptidoglycan synthesis and fosfomycin resistance. J Bacteriol 2003; 185: 1218-28.
82 Chopra I, Storey C, Falla TJ. et al. Antibiotics, peptidoglycan synthesis and genomics: the chlamydial anomaly revisited. Microbiology 1998; 144: 2673-8.
83 Fox A, Rogers JC, Gilbart J. et al. Muramic acid is not detectable in Chlamydia psittaci or Chlamydia trachomatis by gas chromatography-mass spectrometry. Infect Immun 1990; 58: 835-7.
84 Moulder JW. Why is Chlamydia sensitive to penicillin in the absence of peptidoglycan?. Infect Agents Dis 1993; 2: 87-99.
85 Bavoil PM, Hsia R, Ojcius DM. Closing in on Chlamydia and its intracellular bag of tricks. Microbiology 2000; 146: 2723-31.
86 Hsia RC, Pannekoek Y, Ingerowski E. et al. Type III secretion genes identify a putative virulence locus of Chlamydia. Mol Microbiol 1997; 25: 351-9.
87 Stephens RS, Kalman S, Lammel C. et al. Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis. Science 1998; 282: 754-9.
88 Zhong G, Fan P, Ji H. et al. Identification of a chlamydial protease-like activity factor responsible for the degradation of host transcription factors. J Exp Med 2001; 193: 935-42.
89 Heuer D, Brinkmann V, Meyer TF. et al. Expression and translocation of chlamydial protease during acute and persistent infection of the epithelial HEp-2 cells with Chlamydophila (Chlamydia) pneumoniae. Cell Microbiol 2003; 5: 315-22.
90 Pauleau AL, Murray PJ. Role of nod2 in the response of macrophages to toll-like receptor agonists. Mol Cell Biol 2003; 23: 7531-9.
91 Krull M, Klucken AC, Wuppermann FN. et al. Signal transduction pathways activated in endothelial cells following infection with Chlamydia pneumoniae . J Immunol 1999; 162: 4834-41.
92 Azenabor AA, Chaudhry AU, Yang S. Macrophage L-type Ca2+ channel antagonists alter Chlamydia pneumoniae MOMP and HSP-60 mRNA gene expression, and improve antibiotic susceptibility. Immunobiology 2003; 207: 237-45.
93 Azenabor AA, Yang S, Job G. et al. Elicitation of reactive oxygen species in Chlamydia pneumoniaestimulated macrophages: a Ca(2+)-dependent process involving simultaneous activation of NADPH oxidase and cytochrome oxidase genes. Med Microbiol Immunol 2005; 194: 91-103.
94 Wissel H, Muller T, Rudiger M. et al. Contact of Chlamydophila pneumoniae with type II cell triggers activation of calcium-mediated NF-[kappa]B pathway. Biochimica et Biophysica Acta 2005; 1743: 37-48.
95 Kaukoranta-Tolvanen SS, Ronni T, Leinonen M. et al. Expression of adhesion molecules on endothelial cells stimulated by Chlamydia pneumoniae . Microb Pathog 1996; 21: 407-11.
96 Dechend R, Maass M, Gieffers J. et al. Chlamydia pneumoniae infection of vascular smooth muscle and endothelial cells activates NF-kappaB and induces tissue factor and PAI-1 expression: a potential link to accelerated arteriosclerosis. Circulation 1999; 100: 1369-73.
97 Kothe H, Dalhoff K, Rupp J. et al. Hydroxymethylglutaryl coenzyme A reductase inhibitors modify the inflammatory response of human macrophages and endothelial cells infected with Chlamydia pneumoniae . Circulation 2000; 101: 1760-3.
98 Summersgill JT, Molestina RE, Miller RD. et al. Interactions of Chlamydia pneumoniae with human endothelial cells. J Infect Dis 2000; 181 (Suppl. 03) S479-S482.
99 Coombes BK, Mahony JB. cDNA array analysis of altered gene expression in human endothelial cells in response to Chlamydia pneumoniae infection. Infect Immun 2001; 69: 1420-7.
100 Donath B, Fischer C, Page S. et al. Chlamydia pneumoniae activates IKK/I kappa B-mediated signaling, which is inhibited by 4-HNE and following primary exposure. Atherosclerosis 2002; 165: 79-88.
101 Dechend R, Gieffers J, Dietz R. et al. Hydroxymethylglutaryl coenzyme A reductase inhibition reduces Chlamydia pneumoniae-induced cell interaction and activation. Circulation 2003; 108: 261-5.
102 Vielma SA, Krings G, Lopes-Virella MF. Chlamydophila pneumoniae induces ICAM-1 expression in human aortic endothelial cells via protein kinase C-dependent activation of nuclear factor-kappaB. Circ Res 2003; 92: 1130-7.
103 Molestina RE, Miller RD, Lentsch AB. et al. Requirement for NF-kappaB in transcriptional activation of monocyte chemotactic protein 1 by Chlamydia pneumoniae in human endothelial cells. Infect Immun 2000; 68: 4282-8.
104 Miller SA, Selzman CH, Shames BD. et al. Chlamydia pneumoniae activates nuclear factor kappaB and activator protein 1 in human vascular smooth muscle and induces cellular proliferation. J Surg Res 2000; 90: 76-81.
105 Rupp J, Hellwig-Burgel T, Wobbe V. et al. Chlamydia pneumoniae infection promotes a proliferative phenotype in the vasculature through Egr-1 activation in vitro and in vivo. Proc Natl Acad Sci U S A 2005; 102: 3447-52.
106 Al Younes HM, Rudel T, Brinkmann V. et al. Low iron availability modulates the course of Chlamydia pneumoniae infection. Cell Microbiol 2001; 3: 427-37.
107 Pantoja LG, Miller RD, Ramirez JA. et al. Characterization of Chlamydia pneumoniae persistence in HEp-2 cells treated with gamma interferon. Infect Immun 2001; 69: 7927-32.
108 Sakash JB, Byrne GI, Lichtman A. et al. Cytokines induce indoleamine 2,3-dioxygenase expression in human atheroma-asociated cells: implications for persistent Chlamydophila pneumoniae infection. Infect Immun 2002; 70: 3959-61.
109 Byrne GI, Ojcius DM. Chlamydia and apoptosis: life and death decisions of an intracellular pathogen. Nat Rev Microbiol 2004; 2: 802-8.
110 May AE, Redecke V, Gruner S. et al. Recruitment of Chlamydia pneumoniae-infected macrophages to the carotid artery wall in noninfected, nonatherosclerotic mice. Arterioscler Thromb Vasc Biol 2003; 23: 789-94.