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Immune regulation in atherosclerosis and the hygiene hypothesis

  • Hafid Ait-Oufella
  • Alain Tedgui
  • Ziad Mallat
Part of the Progress in Inflammation Research book series (PIR)

Abstract

Atherosclerosis is a chronic inflammatory disease of the arterial wall where both innate and adaptive immune responses contribute to disease initiation and progression. The hygiene hypothesis implies that dysregulation of the immune response has led to increased susceptibility to immuno-inflammatory diseases. Recent studies established that subtypes of T cells, regulatory T cells, actively involved in the maintenance of immunological tolerance, inhibit the development and progression of atherosclerosis. Here, we review the immune regulatory pathways of atherosclerosis and discuss the potential implication of pathogens and their associated molecular patterns in the regulation of the immuno-inflammatory response of atherosclerosis.

Keywords

Treg Cell Arterioscler Thromb Vasc Biol Cardiac Allograft Vasculopathy Hygiene Hypothesis Atherosclerotic Lesion Development 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Bonow RO (2002) Primary prevention of cardiovascular disease: a call to action. Circulation 106: 3140–3141PubMedCrossRefGoogle Scholar
  2. 2.
    Lopez AD, Murray CC (1998) The global burden of disease, 1990–2020. Nat Med 4: 1241–1243PubMedCrossRefGoogle Scholar
  3. 3.
    Skalen K, Gustafsson M, Rydberg EK, Hulten LM, Wiklund O, Innerarity TL, Boren J (2002) Subendothelial retention of atherogenic lipoproteins in early atherosclerosis. Nature 417: 750–754PubMedCrossRefGoogle Scholar
  4. 4.
    Eriksson EE, Xie X, Werr J, Thoren P, Lindbom L (2001) Importance of primary capture and L-selectin-dependent secondary capture in leukocyte accumulation in inflammation and atherosclerosis in vivo J Exp Med 194: 205–218PubMedCrossRefGoogle Scholar
  5. 5.
    Smith JD, Trogan E, Ginsberg M, Grigaux C, Tian J, Miyata M (1995) Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E. Proc Natl Acad Sci USA 92: 8264–8268PubMedCrossRefGoogle Scholar
  6. 6.
    Peiser L, Mukhopadhyay S, Gordon S (2002) Scavenger receptors in innate immunity. Curr Opin Immunol 14: 123–128PubMedCrossRefGoogle Scholar
  7. 7.
    Janeway CA, Jr., Medzhitov R (2002). Innate immune recognition. Annu Rev Immunol 20: 197–216PubMedCrossRefGoogle Scholar
  8. 8.
    Binder CJ, Chang MK, Shaw PX, Miller YI, Hartvigsen K, Dewan A, Witztum JL (2002) Innate and acquired immunity in atherogenesis. Nat Med 8: 1218–1226PubMedCrossRefGoogle Scholar
  9. 9.
    Dansky HM, Charlton SA, Harper MM, Smith JD (1997) T and B lymphocytes play a minor role in atherosclerotic plaque formation in the apolipoprotein E-deficient mouse. Proc Natl Acad Sci USA 94: 4642–4646PubMedCrossRefGoogle Scholar
  10. 10.
    Daugherty A, Pure E, Delfel-Butteiger D, Chen S, Leferovich J, Roselaar SE, Rader DJ (1997) The effects of total lymphocyte deficiency on the extent of atherosclerosis in apolipoprotein E−/− mice. J Clin Invest 100: 1575–1580PubMedCrossRefGoogle Scholar
  11. 11.
    Zhou X, Nicoletti A, Elhage R, Hansson GK (2000) Transfer of CD4(+) T cells aggravates atherosclerosis in immunodeficient a polipoprotein E knockout mice. Circulation 102: 2919–2922PubMedGoogle Scholar
  12. 12.
    Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K (2000) Immunobiology of dendritic cells. Annu Rev Immunol 18: 767–811PubMedCrossRefGoogle Scholar
  13. 13.
    Maldonado-Lopez R, De Smedt T, Michel P, Godfroid J, Pajak B, Heirman C, Thielemans K, Leo O, Urbain J, Moser M (1999) CD8alpha+ and CD8alpha subclasses of dendritic cells direct the development of distinct T helper cells in vivo. J Exp Med 189: 587–592PubMedCrossRefGoogle Scholar
  14. 14.
    Mach F, Schönbeck U, Sukhova GK, Atkinson E, Libby P (1998) Reduction of atherosclerosis in mice by inhibition of CD40 signalling. Nature 394: 200–203PubMedCrossRefGoogle Scholar
  15. 15.
    de Nooijer R, von der Thusen JH, Verkleij CJ, Kuiper J, Jukema JW, van der Wall EE, van Berkel JC, Biessen EA (2004) Overexpression of IL-18 decreases intimal collagen content and promotes a vulnerable plaque phenotype in apolipoprotein-E-deficient mice. Arterioscler Thromb Vasc Biol 24: 2313–2319PubMedCrossRefGoogle Scholar
  16. 16.
    Buono C, Binder CJ, Stavrakis G, Witztum JL, Glimcher LH, Lichtman AH (2005) T-bet deficiency reduces atherosclerosis and alters plaque antigen-specific immune responses. Proc Natl Acad Sci USA 102: 1596–1601PubMedCrossRefGoogle Scholar
  17. 17.
    Mallat Z, Corbaz A, Scoazec A, Graber P, Alouani S, Esposito B, Humbert Y, Chvatchko Y, Tedgui A (2001) Interleukin-18/interleukin-18 binding protein signaling modulates atherosclerotic lesion development and stability Circ Res 89:E41–45PubMedCrossRefGoogle Scholar
  18. 18.
    Schonbeck U, Sukhova GK, Shimizu K, Mach F, Libby P (2000) Inhibition of CD40 signaling limits evolution of established atherosclerosis in mice. Proc Natl Acad Sci USA 97: 7458–7463PubMedCrossRefGoogle Scholar
  19. 19.
    Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392: 245–252PubMedCrossRefGoogle Scholar
  20. 20.
    Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH (2000) A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100: 655–669PubMedCrossRefGoogle Scholar
  21. 21.
    Zhou X, Paulsson G, Stemme S, Hansson GK (1998) Hypercholesterolemia is associated with a T helper (Th) 1/Th2 switch of the autoimmune response in atherosclerotic apo E-knockout mice. J Clin Invest 101: 1717–1725PubMedCrossRefGoogle Scholar
  22. 22.
    Caligiuri G, Nicoletti A, Poirier B, Hansson GK (2002) Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice. J Clin Invest 109: 745–753PubMedGoogle Scholar
  23. 23.
    Palinski W, Miller E, Witztum JL (1995) Immunization of low density lipoprotein (LDL) receptor-deficient rabbits with homologous malondialdehyde-modified LDL reduces atherogenesis. Proc Natl Acad Sci USA 92: 821–825PubMedCrossRefGoogle Scholar
  24. 24.
    Freigang S, Horkko S, Miller E, Witztum JL, Palinski W (1998) Immunization of LDL receptor-deficient mice with homologous malondialdehyde-modified and native LDL reduces progression of atherosclerosis by mechanisms other than induction of high titers of antibodies to oxidative neoepitopes. Arterioscler Thromb Vasc Biol 18: 1972–1982PubMedGoogle Scholar
  25. 25.
    George J, Afek A, Gilburd B, Levkovitz H, Shaish A, Goldberg I, Kopolovic Y, Wick G, Shoenfeld Y, Harats D (1998) Hyperimmunization of apo-E-deficient mice with homologous malondialdehyde low-density lipoprotein suppresses early atherogenesis. Atherosclerosis 138: 147–152PubMedCrossRefGoogle Scholar
  26. 26.
    Binder CJ, Hartvigsen K, Chang MK, Miller M, Broide D, Palinski W, Curtiss LK, Corr M, Witztum JL (2004) IL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL and protects from atherosclerosis. J Clin Invest 114: 427–437PubMedGoogle Scholar
  27. 27.
    Binder CJ, Shaw PX, Chang MK, Boullier A, Hartvigsen K, Horkko S, Miller YI, Woelkers DA, Corr M, Witztum JL (2005) The role of natural antibodies in atherogenesis. J Lipid Res 46: 1353–1363PubMedCrossRefGoogle Scholar
  28. 28.
    Pinderski LJ, Fischbein MP, Subbanagounder G, Fishbein MC, Kubo N, Cheroutre H, Curtiss LK, Berliner JA, Boisvert WA (2002) Overexpression of interleukin-10 by activated T lymphocytes inhibits atherosclerosis in LDL receptor-deficient Mice by altering lymphocyte and macrophage phenotypes. Circ Res 90: 1064–1071PubMedCrossRefGoogle Scholar
  29. 29.
    Huber SA, Sakkinen P, David C, Newell MK, Tracy RP (2001) T helper-cell phenotype regulates atherosclerosis in mice under conditions of mild hypercholesterolemia. Circulation 103: 2610–2616PubMedGoogle Scholar
  30. 30.
    King VL, Szilvassy SJ, Daugherty A (2002) Interleukin-4 deficiency decreases atherosclerotic lesion formation in a site-specific manner in female LDL receptor−/− mice Arterioscler Thromb Vasc Biol 22: 456–461PubMedCrossRefGoogle Scholar
  31. 31.
    Davenport P, Tipping PG (2003) The role of interleukin-4 and interleukin-12 in the progression of atherosclerosis in apolipoprotein E-deficient mice. Am J Pathol 163: 1117–1125PubMedGoogle Scholar
  32. 32.
    Mallat Z, Gojova A, Marchiol-Fournigault C, Esposito B, Kamate C, Merval R, Fradelizi D, Tedgui A (2001) Inhibition of transforming growth factor-beta signaling accelerates atherosclerosis and induces an unstable plaque phenotype in mice. Circ Res 89: 930–934PubMedCrossRefGoogle Scholar
  33. 33.
    Mallat Z, Besnard S, Duriez M, Deleuze V, Emmanuel F, Bureau, MF, Soubrier F, Esposito B, Duez H, Fievet C et al (1999) Protective role of interleukin-10 in atherosclerosis. Circ Res 85: e17–24PubMedGoogle Scholar
  34. 34.
    Davidson NJ, Leach MW, Fort MM, Thompson-Snipes L, Kuhn R, Muller W, Berg DJ, Rennick DM (1996) T helper cell 1-type CD4+ T cells, but not B cells, mediate colitis in interleukin 10-deficient mice. J Exp Med 184: 241–251PubMedCrossRefGoogle Scholar
  35. 35.
    Asseman C, Mauze S, Leach MW, Coffman RL, Powrie F (1999) An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J Exp Med 190: 995–1004PubMedCrossRefGoogle Scholar
  36. 36.
    Wakkach A, Fournier N, Brun V, Breittmayer JP, Cottrez F, Groux H (2003) Characterization of dendritic cells that induce tolerance and T regulatory 1 cell differentiation in vivo. Immunity 18: 605–617PubMedCrossRefGoogle Scholar
  37. 37.
    Caligiuri G, Rudling M, Ollivier V, Jacob MP, Michel JB, Hansson GK, Nicoletti A (2003) Interleukin-10 deficiency increases a therosclerosis, thrombosis, and low-density lipoproteins in apolipoprotein E knockout mice. Mol Med 9: 10–17PubMedGoogle Scholar
  38. 38.
    Potteaux S, Esposito B, van Oostrom O, Brun V, Ardouin P, Groux H, Tedgui A, Mallat Z (2004) Leukocyte-derived interleukin 10 is required for protection against atherosclerosis in low-density lipoprotein receptor knockout mice. Arterioscler Thromb Vasc Biol 24: 1474–1478PubMedCrossRefGoogle Scholar
  39. 39.
    Von Der Thusen JH, Kuiper J Fekkes ML, De Vos P, Van Berkel TJ, Biessen EA (2001) Attenuation of atherogenesis by systemic and local adenovirus-mediated gene transfer of interleukin-10 in LDLr−/− mice. Faseb J 15: 2730–2732Google Scholar
  40. 40.
    Hagenbaugh A, Sharma S, Dubinett SM, Wei SH, Aranda R, Cheroutre H, Fowell DJ, Binder S, Tsao B, Locksley RM et al (1997) Altered immune responses in interleukin 10 transgenic mice. J Exp Med 185: 2101–2110PubMedCrossRefGoogle Scholar
  41. 41.
    Mallat Z, Gojova A, Brun V, Esposito B, Fournier N, Cottrez F, Tedgui A, Groux H. (2003) Induction of a regulatory T cell type 1 response reduces the development of atherosclerosis in apolipoprotein E-knockout mice. Circulation 108: 1232–1237PubMedCrossRefGoogle Scholar
  42. 42.
    Ait-Oufella H, Horvat B, Kerdiles Y, Herbin O, Gourdy P, Khallou-Laschet J, Merval R, Esposito B, Tedgui A, Mallat Z. (2007) Measles virus nucleoprotein induces a regulatory immune response and reduces atherosclerosis in mice. Circulation 116: 1707–1713PubMedCrossRefGoogle Scholar
  43. 43.
    Kulkarni AB, Karlsson S (1993) Transforming growth factor-beta 1 knockout mice. A mutation in one cytokine gene causes a dramatic inflammatory disease. Am J Pathol 143: 3–9PubMedGoogle Scholar
  44. 44.
    Shull MM, Ormsby I, Kier AB, Pawlowski S, Diebold RJ, Yin M, Allen R, Sidman C, Proetzel G, Calvin D et al (1992) Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 359: 693–699PubMedCrossRefGoogle Scholar
  45. 45.
    Li MO, Wan YY, Sanjabi S, Robertson AK, Flavell RA (2006) Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol 24: 99–146PubMedCrossRefGoogle Scholar
  46. 46.
    Cobbold SP, Castejon R, Adams E, Zelenika D, Graca L, Humm S, Waldmann H (2004) Induction of foxP3+ regulatory T cells in the periphery of T cell receptor transgenic mice tolerized to transplants. J Immunol 172: 6003–6010PubMedGoogle Scholar
  47. 47.
    Lutgens E, Gijbels M, Smook M, Heeringa P, Gotwals P, Koteliansky VE, Daemen MJ (2002) Transforming growth factor-beta mediates balance between inflammation and fibrosis during plaque progression. Arterioscler Thromb Vasc Biol 22: 975–982PubMedCrossRefGoogle Scholar
  48. 48.
    Grainger DJ, Mosedale DE, Metcalfe JC, Bottinger EP (2000) Dietary fat and reduced levels of TGFbeta1 act synergistically to promote activation of the vascular endothelium and formation of lipid lesions. J Cell Sci 113 (Pt 13): 2355–2361PubMedGoogle Scholar
  49. 49.
    Gojova A, Brun V, Esposito B, Cottrez F, Gourdy P, Ardouin P, Tedgui A, Mallat Z, Groux H (2003) Specific abrogation of transforming growth factor-beta signaling in T cells alters atherosclerotic lesion size and composition in mice. Blood 102: 4052–4058PubMedCrossRefGoogle Scholar
  50. 50.
    Robertson AK, Rudling M, Zhou X, Gorelik L, Flavell RA, Hansson GK (2003) Disruption of TGF-beta signaling in T cells accelerates atherosclerosis. J Clin Invest 112: 1342–1350PubMedGoogle Scholar
  51. 51.
    Smith DA, Irving SD, Sheldon J, Cole D, Kaski JC (2001) Serum levels of the antinflammatory cytokine interleukin-10 are decreased in patients with unstable angina. Circulation 104: 746–749PubMedCrossRefGoogle Scholar
  52. 52.
    Grainger DJ, Kemp PR, Metcalfe JC, Liu AC, Lawn RM, Williams NR, Grace AA, Schofield PM, Chauhan A (1995) The serum concentration of active transforming growth factor-beta is severely depressed in advanced atherosclerosis. Nat Med 1: 74–79PubMedCrossRefGoogle Scholar
  53. 53.
    Ait-Oufella H, Salomon BL, Potteaux S, Robertson AK, Gourdy P, Zoll J, Merval R, Esposito B, Cohen JL, Fisson, S et al (2006) Natural regulatory T cells control the development of atherosclerosis in mice. Nat Med 12: 178–180PubMedCrossRefGoogle Scholar
  54. 54.
    Mor A, Planer D, Luboshits G, Afek A, Metzger S, Chajek-Shaul T, Keren G, George J (2007) Role of naturally occurring CD4+ CD25+ regulatory T cells in experimental atherosclerosis. Arterioscler Thromb Vasc Biol 27: 893–900PubMedCrossRefGoogle Scholar
  55. 55.
    Gotsman I, Grabie N, Gupta R, Dacosta R, MacConmara M, Lederer J, Sukhova G, Witztum JL, Sharpe AH, Lichtman AH (2006) Impaired regulatory T-cell response and enhanced atherosclerosis in the absence of inducible costimulatory molecule. Circulation 114: 2047–2055PubMedCrossRefGoogle Scholar
  56. 56.
    Heller EA, Liu E, Tager AM, Yuan Q, Lin AY, Ahluwalia N, Jones K, Koehn SL, Lok VM, Aikawa E et al (2006) Chemokine CXCL10 promotes atherogenesis by modulating the local balance of effector and regulatory T cells. Circulation 113: 2301–2312PubMedCrossRefGoogle Scholar
  57. 57.
    Mor A, Luboshits G, Planer D, Keren G, George J (2006) Altered status of CD4(+) CD25(+) regulatory T cells in patients with acute coronary syndromes. Eur Heart J 27: 2530–2537PubMedCrossRefGoogle Scholar
  58. 58.
    de Boer OJ, van der Meer JJ, Teeling P, van der Loos CM, van der Wal AC (2007) Low numbers of FOXP3 positive regulatory T cells are present in all developmental stages of human atherosclerotic lesions. PLoS ONE 2: e779PubMedCrossRefGoogle Scholar
  59. 59.
    Danesh J (2005) Antibiotics in the prevention of heart attacks. Lancet 365: 365–367PubMedGoogle Scholar
  60. 60.
    Epstein SE, Zhou YF, Zhu J (1999) Infection and atherosclerosis: emerging mechanistic paradigms. Circulation 100: e20–28PubMedGoogle Scholar
  61. 61.
    Zhou YF, Leon MB, Waclawiw MA, Popma JJ, Yu ZX, Finkel T, Epstein SE (1996) Association between prior cytomegalovirus infection and the risk of restenosis after coronary atherectomy. N Engl J Med 335: 624–630PubMedCrossRefGoogle Scholar
  62. 62.
    Hendrix MG, Salimans MM, van Boven CP, Bruggeman CA (1990) High prevalence of latently present cytomegalovirus in arterial walls of patients suffering from grade III atherosclerosis. Am J Pathol 136: 23–28PubMedGoogle Scholar
  63. 63.
    Lemstrom K, Sihvola R, Bruggeman C, Hayry P, Koskinen P (1997) Cytomegalovirus infection-enhanced cardiac allograft vasculopathy is abolished by DHPG prophylaxis in the rat. Circulation 95: 2614–2616PubMedGoogle Scholar
  64. 64.
    Streblow DN, Kreklywich C, Yin Q, De La Melena VT, Corless CL, Smith PA, Brakebill C, Cook JW, Vink C, Bruggeman CA et al (2003) Cytomegalovirus-mediated upregulation of chemokine expression correlates with the acceleration of chronic rejection in rat heart transplants. J Virol 77: 2182–2194PubMedCrossRefGoogle Scholar
  65. 65.
    Sedmak DD, Knight DA, Vook NC, Waldman JW (1994) Divergent patterns of ELAM-1, ICAM-1, and VCAM-1 expression on cytomegalovirus-infected endothelial cells. Transplantation 58: 1379–1385PubMedCrossRefGoogle Scholar
  66. 66.
    Fabricant CG, Fabricant J (1999) Atherosclerosis induced by infection with Marek’s disease herpesvirus in chickens. Am Heart J 138: S465–468CrossRefGoogle Scholar
  67. 67.
    Hsich E, Zhou YF, Paigen B, Johnson TM, Burnett MS, Epstein SE (2001) Cytomegalovirus infection increases development of atherosclerosis in Apolipoprotein-E knockout mice. Atherosclerosis 156: 23–28PubMedCrossRefGoogle Scholar
  68. 68.
    Muhlestein JB, Horne BD, Carlquist JF, Madsen TE, Bair TL, Pearson RR, Anderson JL (2000) Cytomegalovirus seropositivity and C-reactive protein have independent and combined predictive value for mortality in patients with angiographically demonstrated coronary artery disease. Circulation 102: 1917–1923PubMedGoogle Scholar
  69. 69.
    Prosch S, Wendt CE, Reinke P, Priemer C, Oppert M, Kruger DH, Volk HD, Docke WD (2000) A novel link between stress and human cytomegalovirus (HCMV) infection: sympathetic hyperactivity stimulates HCMV activation. Virology 272: 357–365PubMedCrossRefGoogle Scholar
  70. 70.
    Saikku P, Leinonen M, Mattila K, Ekman MR, Nieminen MS, Makela PH, Huttunen JK, Valtonen V (1988) Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet 2: 983–986PubMedCrossRefGoogle Scholar
  71. 71.
    Kuo CC, Gown AM, Benditt EP, Grayston JT (1993) Detection of Chlamydia pneumoniae in aortic lesions of atherosclerosis by immunocytochemical stain. Arterioscler Thromb 13: 1501–1504PubMedGoogle Scholar
  72. 72.
    O’Connor CM, Dunne MW, Pfeffer MA, Muhlestein JB, Yao L, Gupta S, Benner RJ, Fisher MR, Cook TD (2003) Azithromycin for the secondary prevention of coronary heart disease events: the WIZARD study: a randomized controlled trial. Jama 290: 1459–1466PubMedCrossRefGoogle Scholar
  73. 73.
    Cercek B, Shah PK, Noc M, Zahger D, Zeymer U, Matetzky S, Maurer G, Mahrer P (2003) Effect of short-term treatment iwth 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 361: 809–813PubMedCrossRefGoogle Scholar
  74. 74.
    Cannon CP, Braunwald E, McCabe CH, Grayston JT, Muhlestein B, Giugliano RP, Cairns R, Skene AM (2005) Antibiotic treatment of Chlamydia pneumoniae after acute coronary syndrome. N Engl J Med 352: 1646–1654PubMedCrossRefGoogle Scholar
  75. 75.
    Grayston JT, Kronmal RA, Jackson LA, Parisi AF, Muhlestein JB, Cohen JD, Rogers WJ, Crouse JR, Borrowdale SL, Schron E et al (2005) Azithromycin for the secondary prevention of coronary events. N Engl J Med 352: 1637–1645PubMedCrossRefGoogle Scholar
  76. 76.
    Moazed TC, Campbell LA, Rosenfeld ME, Grayston JT, Kuo CC (1999) Chlamydia pneumoniae infection accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice. J Infect Dis 180: 238–241PubMedCrossRefGoogle Scholar
  77. 77.
    Hu H, Pierce GN, Zhong G (1999) The atherogenic effects of chlamydia are dependent on serum cholesterol and specific to Chlamydia pneumoniae. J Clin Invest 103: 747–753PubMedCrossRefGoogle Scholar
  78. 78.
    Caligiuri G, Rottenberg M, Nicoletti A, Wigzell H, Hansson GK (2001) Chlamydia pneumoniae infection does not induce or modify atherosclerosis in mice. Circulation 103: 2834–2838PubMedGoogle Scholar
  79. 79.
    Wright SD, Burton C, Hernandez M, Hassing H, Montenegro J, Mundt S, Patel S, Card DJ, Hermanowski-Vosatka A, Bergstrom JD et al (2000) Infectious agents are not necessary for murine atherogenesis. J Exp Med 191: 1437–1442PubMedCrossRefGoogle Scholar
  80. 80.
    Yang X, Coriolan D, Murthy V, Schultz K, Golenbock DT, Beasley D (2005) Proinflammatory phenotype of vascular smooth muscle cells: role of efficient Toll-like receptor 4 signaling. Am J Physiol Heart Circ Physiol 289: H1069–1076PubMedCrossRefGoogle Scholar
  81. 81.
    Krutzik SR, Tan B, Li H, Ochoa MT, Liu PT, Sharfstein SE, Graeber TG, Sieling PA, Liu YJ, Rea TH et al (2005) TLR activation triggers the rapid differentiation of monocytes into macrophages and dendritic cells. Nat Med 11: 653–660PubMedCrossRefGoogle Scholar
  82. 82.
    Mullick AE, Tobias PS, Curtiss LK (2005) Modulation of atherosclerosis in mice by Toll-like receptor 2. J Clin Invest 115: 3149–3156PubMedCrossRefGoogle Scholar
  83. 83.
    Schoneveld AH, Oude Nijhuis MM, van Middelaar B, Laman JD, de Kleijn DP, Pasterkamp G (2005) Toll-like receptor 2 stimulation induces intimal hyperplasia and atherosclerotic lesion development. Cardiovasc Res 66: 162–169PubMedCrossRefGoogle Scholar
  84. 84.
    Laman JD, Schoneveld AH, Moll FL, van Meurs M, Pasterkamp G (2002) Significance of peptidoglycan, a proinflammatory bacterial antigen in atherosclerotic arteries and its association with vulnerable plaques. Am J Cardiol 90: 119–123PubMedCrossRefGoogle Scholar
  85. 85.
    Ott SJ, El Mokhatari NE, Musfeldt M, Hellmig S, Freitag S, Rehman A, Kuhbacher T, Nikolaus S, Namsolleck P, Blaut M et al (2006) Detection of diverse bacterial signatures in atherosclerotic lesions of patients with coronary heart disease. Circulation 113: 929–937PubMedCrossRefGoogle Scholar
  86. 86.
    Michelsen KS, Wong MH, Shah PK, Zhang W, Yano J, Doherty TM, Akira S, Rajavashisth TB, Arditi M (2004) Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E. Proc Natl Acad Sci USA 101: 10679–10684PubMedCrossRefGoogle Scholar
  87. 87.
    Edfeldt K, Swedenborg J, Hansson GK, Yan ZQ (2002) Expression of toll-like receptors in human atherosclerotic lesions: a possible pathway for plaque activation. Circulation 105: 1158–1161PubMedGoogle Scholar
  88. 88.
    Cao F, Castrillo A, Tontonoz P, Re F, Byrne GI (2007) Chlamydia pneumoniae-induced macrophage foam cell formation is mediated by Toll-like receptor 2. Infect Immun 75: 753–759PubMedCrossRefGoogle Scholar
  89. 89.
    Lehtonen L, Eerola E, Oksman P, Toivanen P (1995) Muramic acid in peripheral blood leukocytes of healthy human subjects. J Infect Dis 171: 1060–1064PubMedGoogle Scholar
  90. 90.
    Wiedermann CJ, Kiechl S, Dunzendorfer S, Schratzberger P, Egger G, Oberhollenzer F, Willeit J (1999) Association of endotoxemia with carotid atherosclerosis and cardiovascular disease: prospective results from the Bruneck Study. J Am Coll Cardiol 34: 1975–1981PubMedCrossRefGoogle Scholar
  91. 91.
    Erridge C, Spickett CM, Webb DJ (2007) Non-enterobacterial endotoxins stimulate human coronary artery but not venous endothelial cell activation via Toll-like receptor 2. Cardiovasc Res 73: 181–189PubMedCrossRefGoogle Scholar
  92. 92.
    Demmer RT, Desvarieux M (2006) Periodontal infections and cardiovascular disease: the heart of the matter. J Am Dent Assoc (137) Suppl: 14S–20S; quiz 38SGoogle Scholar
  93. 93.
    Gagliardi MC, Sallusto F, Marinaro M, Langenkamp A, Lanzavecchia A, De Magistris MT (2000) Cholera toxin induces maturation of human dendritic cells and licences them for Th2 priming. Eur J Immunol 30: 2394–2403PubMedCrossRefGoogle Scholar
  94. 94.
    Whelan M, Harnett MM, Houston KM, Patel V, Harnett W, Rigley KP (2000) A filarial nematode-secreted product signals dendritic cells to acquire a phenotype that drives development of Th2 cells. J Immunol 164: 6453–6460PubMedGoogle Scholar
  95. 95.
    McGuirk P, McCann C, Mills KH (2002) Pathogen-specific T regulatory 1 cells induced in the respiratory tract by a bacterial molecule that stimulates interleukin 10 production by dendritic cells: a novel strategy for evasion of protective T helper type 1 responses by Bordetella pertussis. J Exp Med 195: 221–231PubMedCrossRefGoogle Scholar
  96. 96.
    Cheng X, Chen Y, Xie JJ, Yao R, Yu X, Liao MY, Ding YJ, Tang TT, Liao YH, Cheng Y (2008) Suppressive oligodeoxynucleotides inhibit atherosclerosis in ApoE(-/-) mice through modulation of Th1/Th2 balance. J Mol Cell Cardiol 45: 168–175PubMedCrossRefGoogle Scholar
  97. 97.
    Zhou X, Robertson AK, Rudling M, Parini P, Hansson GK (2005) Lesion development and response to immunization reveal a complex role for CD4 in atherosclerosis. Circ Res 96: 427–434PubMedCrossRefGoogle Scholar
  98. 98.
    Hansen PR, Chew M, Zhou J, Daugherty A, Heegaard N, Jensen P, Mouritsen S, Falk E (2001) Freunds adjuvant alone is antiatherogenic in apoE-deficient mice and specific immunization against TNFalpha confers no additional benefit. Atherosclerosis 158: 87–94PubMedCrossRefGoogle Scholar
  99. 99.
    Khallou-Laschet J, Tupin E, Caligiuri G, Poirier B, Thieblemont N, Gaston AT, Vandaele M, Bleton J, Tchapla A, Kaveri SV et al (2006) Atheroprotective effect of adjuvants in apolipoprotein E knockout mice. Atherosclerosis 184: 330–341PubMedCrossRefGoogle Scholar
  100. 100.
    Tian B, Hao J, Zhang Y, Tian L, Yi H, O’Brien TD, Sutherland DE, Hering BJ, Guo Z (2009) Upregulating CD4+CD25+FOXP3+ regulatory T cells in pancreatic lymph nodes in diabetic NOD mice by adjuvant immunotherapy. Transplantation 87: 198–206PubMedCrossRefGoogle Scholar
  101. 101.
    Binder CJ, Horkko S, Dewan A, Chang MK, Kieu EP, Goodyear CS, Shaw PX, Palinski W, Witztum JL, Silverman GJ (2003) Pneumococcal vaccination decreases atherosclerotic lesion formation: molecular mimicry between Streptococcus pneumoniae and oxidized LDL. Nat Med 9: 736–743PubMedCrossRefGoogle Scholar
  102. 102.
    Murray CJ, Lopez AD (1997) Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 349: 1436–1442PubMedCrossRefGoogle Scholar
  103. 103.
    Marie JC, Kehren J, Trescol-Biemont MC, Evlashev A, Valentin H, Walzer T, Tedone R, Loveland B, Nicolas JF, Rabourdin-Combe C et al (2001) Mechanism of measles virus-induced suppression of inflammatory immune responses. Immunity 14: 69–79PubMedCrossRefGoogle Scholar

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© Birkhäuser Verlag Basel/Switzerland 2009

Authors and Affiliations

  • Hafid Ait-Oufella
    • 1
  • Alain Tedgui
    • 1
  • Ziad Mallat
    • 1
  1. 1.Paris Cardiovascular Research Center, INSERM and Assistance Publique-Hôpitaux de ParisHôpital Européen Georges PompidouParisFrance

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