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Open Access 01-01-2013 | Movement Disorders - Review article

Autoimmunity, dendritic cells and relevance for Parkinson’s disease

Authors: E. Koutsilieri, M. B. Lutz, C. Scheller

Published in: Journal of Neural Transmission | Issue 1/2013

Abstract

Innate and adaptive immune responses in neurodegenerative diseases have become recently a focus of research and discussions. Parkinson’s disease (PD) is a neurodegenerative disorder without known etiopathogenesis. The past decade has generated evidence for an involvement of the immune system in PD pathogenesis. Both inflammatory and autoimmune mechanisms have been recognized and studies have emphasized the role of activated microglia and T-cell infiltration. In this short review, we focus on dendritic cells, on their role in initiation of autoimmune responses, we discuss aspects of neuroinflammation and autoimmunity in PD, and we report new evidence for the involvement of neuromelanin in these processes.

Andersen O, Lygner PE, Bergstrom T, Andersson M, Vahlne A (1993) Viral infections trigger multiple sclerosis relapses: a prospective seroepidemiological study. J Neurol 240:417–422PubMedCrossRef

Bach JF (2005) Infections and autoimmune diseases. J Autoimmun 25(Suppl):74–80PubMedCrossRef

Benkler M, Agmon-Levin N, Shoenfeld Y (2009) Parkinson’s disease, autoimmunity, and olfaction. Int J Neurosci 119:2133–2143PubMedCrossRef

Berer K, Mues M, Koutrolos M, Rasbi ZA, Boziki M, Johner C, Wekerle H, Krishnamoorthy G (2011) Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature 479:538–541PubMedCrossRef

Bianchi FB, Muratori P, Granito A, Pappas G, Ferri S, Muratori L (2007) Hepatitis C and autoreactivity. Dig Liver Dis 39(Suppl 1):S22–S24PubMedCrossRef

Boucquey D, Chalon MP, Sindic CJ, Lamy ME, Laterre C (1990) Herpes simplex virus type 2 meningitis without genital lesions: an immunoblot study. J Neurol 237:285–289PubMedCrossRef

Brigl M, Brenner MB (2004) CD1: antigen presentation and T cell function. Annu Rev Immunol 22:817–890PubMedCrossRef

Buzas EI, Gyorgy B, Pasztoi M, Jelinek I, Falus A, Gabius HJ (2006) Carbohydrate recognition systems in autoimmunity. Autoimmunity 39:691–704PubMedCrossRef

Chastain EM, Miller SD (2012) Molecular mimicry as an inducing trigger for CNS autoimmune demyelinating disease. Immunol Rev 245:227–238PubMedCrossRef

Chen S, Le WD, Xie WJ, Alexianu ME, Engelhardt JI, Siklos L, Appel SH (1998) Experimental destruction of substantia nigra initiated by Parkinson disease immunoglobulins. Arch Neurol 55:1075–1080PubMedCrossRef

Chervonsky AV (2010) Influence of microbial environment on autoimmunity. Nat Immunol 11:28–35PubMedCrossRef

Cravens PD, Lipsky PE (2002) Dendritic cells, chemokine receptors and autoimmune inflammatory diseases. Immunol Cell Biol 80:497–505PubMedCrossRef

de Vos AF, van Meurs M, Brok HP, Boven LA, Hintzen RQ, van der Valk P, Ravid R, Rensing S, Boon L, t Hart BA, Laman JD (2002) Transfer of central nervous system autoantigens and presentation in secondary lymphoid organs. J Immunol 169:5415–5423PubMed

Delogu LG, Deidda S, Delitala G, Manetti R (2011) Infectious diseases and autoimmunity. J Infect Dev Ctries 5:679–687PubMed

Depboylu C, Schafer MK, Arias-Carrion O, Oertel WH, Weihe E, Hoglinger GU (2011) Possible involvement of complement factor C1q in the clearance of extracellular neuromelanin from the substantia nigra in Parkinson disease. J Neuropathol Exp Neurol 70:125–132PubMedCrossRef

Double KL, Rowe DB, Carew-Jones FM, Hayes M, Chan DK, Blackie J, Corbett A, Joffe R, Fung VS, Morris J, Riederer P, Gerlach M, Halliday GM (2009) Anti-melanin antibodies are increased in sera in Parkinson’s disease. Exp Neurol 217:297–301PubMedCrossRef

Ferri S, Muratori L, Lenzi M, Granito A, Bianchi FB, Vergani D (2008) HCV and autoimmunity. Curr Pharm Des 14:1678–1685PubMedCrossRef

Fischer HG, Reichmann G (2001) Brain dendritic cells and macrophages/microglia in central nervous system inflammation. J Immunol 166:2717–2726PubMed

Goverman J (2009) Autoimmune T cell responses in the central nervous system. Nat Rev Immunol 9:393–407PubMedCrossRef

Graham DG (1979) On the origin and significance of neuromelanin. Arch Pathol Lab Med 103:359–362PubMed

Greter M, Heppner FL, Lemos MP, Odermatt BM, Goebels N, Laufer T, Noelle RJ, Becher B (2005) Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat Med 11:328–334PubMedCrossRef

Haahr S, Hollsberg P (2006) Multiple sclerosis is linked to Epstein–Barr virus infection. Rev Med Virol 16:297–310PubMedCrossRef

Huang YM, Xiao BG, Ozenci V, Kouwenhoven M, Teleshova N, Fredrikson S, Link H (1999) Multiple sclerosis is associated with high levels of circulating dendritic cells secreting pro-inflammatory cytokines. J Neuroimmunol 99:82–90PubMedCrossRef

Hughes RA, Cornblath DR (2005) Guillain–Barré syndrome. Lancet 366:1653–1666PubMedCrossRef

Kamradt T, Mitchison NA (2001) Tolerance and autoimmunity. N Engl J Med 344:655–664PubMedCrossRef

Kanter JL, Narayana S, Ho PP, Catz I, Warren KG, Sobel RA, Steinman L, Robinson WH (2006) Lipid microarrays identify key mediators of autoimmune brain inflammation. Nat Med 12:138–143PubMedCrossRef

Karman J, Ling C, Sandor M, Fabry Z (2004) Initiation of immune responses in brain is promoted by local dendritic cells. J Immunol 173:2353–2361PubMed

Kivisakk P, Mahad DJ, Callahan MK, Sikora K, Trebst C, Tucky B, Wujek J, Ravid R, Staugaitis SM, Lassmann H, Ransohoff RM (2004) Expression of CCR7 in multiple sclerosis: implications for CNS immunity. Ann Neurol 55:627–638PubMedCrossRef

Kohl J (2006) The role of complement in danger sensing and transmission. Immunol Res 34:157–176PubMedCrossRef

Kojouharova M, Reid K, Gadjeva M (2010) New insights into the molecular mechanisms of classical complement activation. Mol Immunol 47:2154–2160PubMedCrossRef

Kuijf ML, Samsom JN, van Rijs W, Bax M, Huizinga R, Heikema AP, van Doorn PA, van Belkum A, van Kooyk Y, Burgers PC, Luider TM, Endtz HP, Nieuwenhuis EE, Jacobs BC (2010) TLR4-mediated sensing of Campylobacter jejuni by dendritic cells is determined by sialylation. J Immunol 185:748–755PubMedCrossRef

Lande R, Gafa V, Serafini B, Giacomini E, Visconti A, Remoli ME, Severa M, Parmentier M, Ristori G, Salvetti M, Aloisi F, Coccia EM (2008) Plasmacytoid dendritic cells in multiple sclerosis: intracerebral recruitment and impaired maturation in response to interferon-beta. J Neuropathol Exp Neurol 67:388–401PubMed

Lang GA, Exley MA, Lang ML (2006) The CD1d-binding glycolipid alpha-galactosylceramide enhances humoral immunity to T-dependent and T-independent antigen in a CD1d-dependent manner. Immunology 119:116–125PubMedCrossRef

Langston JW, Ballard P, Tetrud JW, Irwin I (1983) Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219:979–980PubMedCrossRef

Lesage S, Brice A (2009) Parkinson’s disease: from monogenic forms to genetic susceptibility factors. Hum Mol Genet 18:R48–R59PubMedCrossRef

Liu B, Gao HM, Hong JS (2003) Parkinson’s disease and exposure to infectious agents and pesticides and the occurrence of brain injuries: role of neuroinflammation. Environ Health Perspect 111:1065–1073PubMedCrossRef

Ludewig B, Junt T, Hengartner H, Zinkernagel RM (2001) Dendritic cells in autoimmune diseases. Curr Opin Immunol 13:657–662PubMedCrossRef

Lunemann JD, Munz C (2007) Epstein–Barr virus and multiple sclerosis. Curr Neurol Neurosci Rep 7:253–258PubMedCrossRef

Manfredi AA, Capobianco A, Bianchi ME, Rovere-Querini P (2009) Regulation of dendritic- and T-cell fate by injury-associated endogenous signals. Crit Rev Immunol 29:69–86PubMedCrossRef

Matzinger P (2002) The danger model: a renewed sense of self. Science 296:301–305PubMedCrossRef

McGeer PL, McGeer EG (2004) Inflammation and the degenerative diseases of aging. Ann N Y Acad Sci 1035:104–116PubMedCrossRef

McGonagle D, McDermott M (2006) A proposed classification of the immunological diseases. PLoS Med 3:e297PubMedCrossRef

McMahon EJ, Bailey SL, Miller SD (2006) CNS dendritic cells: critical participants in CNS inflammation? Neurochem Int 49:195–203PubMedCrossRef

McMenamin PG (1999) Distribution and phenotype of dendritic cells and resident tissue macrophages in the dura mater, leptomeninges, and choroid plexus of the rat brain as demonstrated in wholemount preparations. J Comp Neurol 405:553–562PubMedCrossRef

Miller SD, Vanderlugt CL, Begolka WS, Pao W, Yauch RL, Neville KL, Katz-Levy Y, Carrizosa A, Kim BS (1997) Persistent infection with Theiler’s virus leads to CNS autoimmunity via epitope spreading. Nat Med 3:1133–1136PubMedCrossRef

Mills KH (2011) TLR-dependent T cell activation in autoimmunity. Nat Rev Immunol 11:807–822PubMed

Morelli AE, Thomson AW (2007) Tolerogenic dendritic cells and the quest for transplant tolerance. Nat Rev Immunol 7:610–621PubMedCrossRef

Munz C, Lunemann JD, Getts MT, Miller SD (2009) Antiviral immune responses: triggers of or triggered by autoimmunity? Nat Rev Immunol 9:246–258PubMedCrossRef

Nores GA, Lardone RD, Comin R, Alaniz ME, Moyano AL, Irazoqui FJ (2008) Anti-GM1 antibodies as a model of the immune response to self-glycans. Biochim Biophys Acta 1780:538–545PubMedCrossRef

Oberlander U, Pletinckx K, Dohler A, Muller N, Lutz MB, Arzberger T, Riederer P, Gerlach M, Koutsilieri E, Scheller C (2011) Neuromelanin is an immune stimulator for dendritic cells in vitro. BMC Neurosci 12:116PubMedCrossRef

Obermeier B, Lovato L, Mentele R, Bruck W, Forne I, Imhof A, Lottspeich F, Turk KW, Willis SN, Wekerle H, Hohlfeld R, Hafler DA, O’Connor KC, Dornmair K (2011) Related B cell clones that populate the CSF and CNS of patients with multiple sclerosis produce CSF immunoglobulin. J Neuroimmunol 233:245–248PubMedCrossRef

Orr CF, Rowe DB, Mizuno Y, Mori H, Halliday GM (2005) A possible role for humoral immunity in the pathogenesis of Parkinson’s disease. Brain 128:2665–2674PubMedCrossRef

Papachroni KK, Ninkina N, Papapanagiotou A, Hadjigeorgiou GM, Xiromerisiou G, Papadimitriou A, Kalofoutis A, Buchman VL (2007) Autoantibodies to alpha-synuclein in inherited Parkinson’s disease. J Neurochem 101:749–756PubMedCrossRef

Pashenkov M, Huang YM, Kostulas V, Haglund M, Soderstrom M, Link H (2001) Two subsets of dendritic cells are present in human cerebrospinal fluid. Brain 124:480–492PubMedCrossRef

Platt AM, Randolph GJ (2010) Does deleting dendritic cells delete autoimmunity? Immunity 33:840–842PubMedCrossRef

Randolph GJ, Beaulieu S, Lebecque S, Steinman RM, Muller WA (1998) Differentiation of monocytes into dendritic cells in a model of transendothelial trafficking. Science 282:480–483PubMedCrossRef

Regner M, Lambert PH (2001) Autoimmunity through infection or immunization? Nat Immunol 2:185–188PubMedCrossRef

Romani L (2008) Parasites and autoimmunity: the case of fungi. Autoimmun Rev 8:129–133PubMedCrossRef

Root-Bernstein R, Vonck J, Podufaly A (2009) Antigenic complementarity between coxsackie virus and streptococcus in the induction of rheumatic heart disease and autoimmune myocarditis. Autoimmunity 42:1–16PubMedCrossRef

Roselli F, Russo I, Fraddosio A, Aniello MS, De Mari M, Lamberti P, Livrea P, Defazio G (2006) Reversible Parkinsonian syndrome associated with anti-neuronal antibodies in acute EBV encephalitis: a case report. Parkinsonism Relat Disord 12:257–260PubMedCrossRef

Rosner S, Giladi N, Orr-Urtreger A (2008) Advances in the genetics of Parkinson’s disease. Acta Pharmacol Sin 29:21–34PubMedCrossRef

Sindic CJ, Boucquey D, Van Antwerpen MP, Baelden MC, Laterre C, Cocito C (1990) Intrathecal synthesis of anti-mycobacterial antibodies in patients with tuberculous meningitis. An immunoblotting study. J Neurol Neurosurg Psychiatry 53:662–666PubMedCrossRef

Stasiolek M, Bayas A, Kruse N, Wieczarkowiecz A, Toyka KV, Gold R, Selmaj K (2006) Impaired maturation and altered regulatory function of plasmacytoid dendritic cells in multiple sclerosis. Brain 129:1293–1305PubMedCrossRef

Steinman RM, Nussenzweig MC (2002) Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc Natl Acad Sci USA 99:351–358PubMedCrossRef

Thomson AW, Robbins PD (2008) Tolerogenic dendritic cells for autoimmune disease and transplantation. Ann Rheum Dis 67(Suppl 3):iii90–96

Uitti RJ, Calne DB (1993) Pathogenesis of idiopathic Parkinsonism. Eur Neurol 33(Suppl 1):6–23PubMedCrossRef

van Duivenvoorde LM, van Mierlo GJ, Boonman ZF, Toes RE (2006) Dendritic cells: vehicles for tolerance induction and prevention of autoimmune diseases. Immunobiology 211:627–632PubMedCrossRef

Whartenby KA, Calabresi PA, McCadden E, Nguyen B, Kardian D, Wang T, Mosse C, Pardoll DM, Small D (2005) Inhibition of FLT3 signaling targets DCs to ameliorate autoimmune disease. Proc Natl Acad Sci USA 102:16741–16746PubMedCrossRef

Wilms H, Rosenstiel P, Sievers J, Deuschl G, Zecca L, Lucius R (2003) Activation of microglia by human neuromelanin is NF-kappaB dependent and involves p38 mitogen-activated protein kinase: implications for Parkinson’s disease. FASEB J 17:500–502PubMed

Yanamandra K, Gruden MA, Casaite V, Meskys R, Forsgren L, Morozova-Roche LA (2011) Alpha-synuclein reactive antibodies as diagnostic biomarkers in blood sera of Parkinson’s disease patients. PLoS ONE 6:e18513PubMedCrossRef

Yuki N, Odaka M (2005) Ganglioside mimicry as a cause of Guillain–Barré syndrome. Curr Opin Neurol 18:557–561PubMedCrossRef

Zajonc DM, Maricic I, Wu D, Halder R, Roy K, Wong CH, Kumar V, Wilson IA (2005) Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity. J Exp Med 202:1517–1526PubMedCrossRef

Zappia M, Crescibene L, Bosco D, Arabia G, Nicoletti G, Bagala A, Bastone L, Napoli ID, Caracciolo M, Bonavita S, Di Costanzo A, Gambardella A, Quattrone A (2002) Anti-GM1 ganglioside antibodies in Parkinson’s disease. Acta Neurol Scand 106:54–57PubMedCrossRef

Zecca L, Costi P, Mecacci C, Ito S, Terreni M, Sonnino S (2000) Interaction of human substantia nigra neuromelanin with lipids and peptides. J Neurochem 74:1758–1765PubMedCrossRef

Zhang W, Phillips K, Wielgus AR, Liu J, Albertini A, Zucca FA, Faust R, Qian SY, Miller DS, Chignell CF, Wilson B, Jackson-Lewis V, Przedborski S, Joset D, Loike J, Hong JS, Sulzer D, Zecca L (2011) Neuromelanin activates microglia and induces degeneration of dopaminergic neurons: implications for progression of Parkinson’s disease. Neurotox Res 19:63–72PubMedCrossRef

Zozulya AL, Clarkson BD, Ortler S, Fabry Z, Wiendl H (2010) The role of dendritic cells in CNS autoimmunity. J Mol Med (Berl) 88:535–544CrossRef

Title: Autoimmunity, dendritic cells and relevance for Parkinson’s disease
Authors: E. Koutsilieri
M. B. Lutz
C. Scheller
Publication date: 01-01-2013
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 1/2013
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-012-0842-7

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Autoimmunity, dendritic cells and relevance for Parkinson’s disease

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