#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Analysis of Behavior and Trafficking of Dendritic Cells within the Brain during Toxoplasmic Encephalitis


Under normal conditions the immune system has limited access to the brain; however, during toxoplasmic encephalitis (TE), large numbers of T cells and APCs accumulate within this site. A combination of real time imaging, transgenic reporter mice, and recombinant parasites allowed a comprehensive analysis of CD11c+ cells during TE. These studies reveal that the CNS CD11c+ cells consist of a mixture of microglia and dendritic cells (DCs) with distinct behavior associated with their ability to interact with parasites or effector T cells. The CNS DCs upregulated several chemokine receptors during TE, but none of these individual receptors tested was required for migration of DCs into the brain. However, this process was pertussis toxin sensitive and dependent on the integrin LFA-1, suggesting that the synergistic effect of signaling through multiple chemokine receptors, possibly leading to changes in the affinity of LFA-1, is involved in the recruitment/retention of DCs to the CNS and thus provides new insights into how the immune system accesses this unique site.


Vyšlo v časopise: Analysis of Behavior and Trafficking of Dendritic Cells within the Brain during Toxoplasmic Encephalitis. PLoS Pathog 7(9): e32767. doi:10.1371/journal.ppat.1002246
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002246

Souhrn

Under normal conditions the immune system has limited access to the brain; however, during toxoplasmic encephalitis (TE), large numbers of T cells and APCs accumulate within this site. A combination of real time imaging, transgenic reporter mice, and recombinant parasites allowed a comprehensive analysis of CD11c+ cells during TE. These studies reveal that the CNS CD11c+ cells consist of a mixture of microglia and dendritic cells (DCs) with distinct behavior associated with their ability to interact with parasites or effector T cells. The CNS DCs upregulated several chemokine receptors during TE, but none of these individual receptors tested was required for migration of DCs into the brain. However, this process was pertussis toxin sensitive and dependent on the integrin LFA-1, suggesting that the synergistic effect of signaling through multiple chemokine receptors, possibly leading to changes in the affinity of LFA-1, is involved in the recruitment/retention of DCs to the CNS and thus provides new insights into how the immune system accesses this unique site.


Zdroje

1. DenkersEYButcherBADel RioLBennounaS 2004 Neutrophils, dendritic cells and Toxoplasma. Int J Parasitol 34 411 421

2. HunterCASuzukiYSubausteCSRemingtonJS 1996 Cells and cytokines in resistance to Toxoplasma gondii. Curr Top Microbiol Immunol 219 113 125

3. HitzigerNDellacasaIAlbigerBBarraganA 2005 Dissemination of Toxoplasma gondii to immunoprivileged organs and role of Toll/interleukin-1 receptor signalling for host resistance assessed by in vivo bioluminescence imaging. Cell Microbiol 7 837 848

4. SuzukiY 2002 Immunopathogenesis of cerebral toxoplasmosis. J Infect Dis 186 Suppl 2 S234 240

5. UnnoASuzukiKXuanXNishikawaYKitohK 2008 Dissemination of extracellular and intracellular Toxoplasma gondii tachyzoites in the blood flow. Parasitol Int 57 515 518

6. KangSSMcGavernDB 2008 Lymphocytic choriomeningitis infection of the central nervous system. Front Biosci 13 4529 4543

7. SuzukiY 2002 Host resistance in the brain against Toxoplasma gondii. J Infect Dis 185 Suppl 1 S58 65

8. Wilson EHHTMrassPJohnBTaitEDWuGF 2009 Behavior of parasite-specific effector CD8+ T cells in the brain and visualization of a kinesis-associated system of reticular fibers. Immunity 30 300 311

9. EngelhardtB 2006 Molecular mechanisms involved in T cell migration across the blood-brain barrier. J Neural Transm 113 477 485

10. DenkersEYGazzinelliRT 1998 Regulation and function of T-cell-mediated immunity during Toxoplasma gondii infection. Clin Microbiol Rev 11 569 588

11. GazzinelliRXuYHienySCheeverASherA 1992 Simultaneous depletion of CD4+ and CD8+ T lymphocytes is required to reactivate chronic infection with Toxoplasma gondii. J Immunol 149 175 180

12. SuzukiYWangXJortnerBSPayneLNiY 2010 Removal of Toxoplasma gondii Cysts from the Brain by Perforin-Mediated Activity of CD8+ T Cells. Am J Pathol 176 1607 1613

13. HouBBensonAKuzmichLDeFrancoALYarovinskyF 2011 Critical coordination of innate immune defense against Toxoplasma gondii by dendritic cells responding via their Toll-like receptors. Proc Natl Acad Sci U S A 108 278 283

14. JohnBHarrisTHTaitEDWilsonEHGreggB 2009 Dynamic Imaging of CD8(+) T cells and dendritic cells during infection with Toxoplasma gondii. PLoS Pathog 5 e1000505

15. LiuCHFanYTDiasAEsperLCornRA 2006 Cutting edge: dendritic cells are essential for in vivo IL-12 production and development of resistance against Toxoplasma gondii infection in mice. J Immunol 177 31 35

16. TaitEDJordanKADupontCDHarrisTHGreggB 2010 Virulence of Toxoplasma gondii is associated with distinct dendritic cell responses and reduced numbers of activated CD8+ T cells. J Immunol 185 1502 1512

17. FischerHGBonifasUReichmannG 2000 Phenotype and functions of brain dendritic cells emerging during chronic infection of mice with Toxoplasma gondii. J Immunol 164 4826 4834

18. FischerHGReichmannG 2001 Brain dendritic cells and macrophages/microglia in central nervous system inflammation. J Immunol 166 2717 2726

19. DeshpandePKingILSegalBM 2007 Cutting edge: CNS CD11c+ cells from mice with encephalomyelitis polarize Th17 cells and support CD25+CD4+ T cell-mediated immunosuppression, suggesting dual roles in the disease process. J Immunol 178 6695 6699

20. McMahonEJBaileySLMillerSD 2006 CNS dendritic cells: critical participants in CNS inflammation? Neurochem Int 49 195 203

21. SuterTBiollazGGattoDBernasconiLHerrenT 2003 The brain as an immune privileged site: dendritic cells of the central nervous system inhibit T cell activation. Eur J Immunol 33 2998 3006

22. IlarreguiJMCrociDOBiancoGAToscanoMASalatinoM 2009 Tolerogenic signals delivered by dendritic cells to T cells through a galectin-1-driven immunoregulatory circuit involving interleukin 27 and interleukin 10. Nat Immunol 10 981 991

23. IlarreguiJMRabinovichGA 2010 Tolerogenic dendritic cells in the control of autoimmune neuroinflammation: an emerging role of protein-glycan interactions. Neuroimmunomodulation 17 157 160

24. BaileySLSchreinerBMcMahonEJMillerSD 2007 CNS myeloid DCs presenting endogenous myelin peptides ‘preferentially’ polarize CD4+ T(H)-17 cells in relapsing EAE. Nat Immunol 8 172 180

25. MillerSDMcMahonEJSchreinerBBaileySL 2007 Antigen presentation in the CNS by myeloid dendritic cells drives progression of relapsing experimental autoimmune encephalomyelitis. Ann N Y Acad Sci 1103 179 191

26. KarmanJChuHHCoDOSeroogyCMSandorM 2006 Dendritic cells amplify T cell-mediated immune responses in the central nervous system. J Immunol 177 7750 7760

27. SantambrogioLBelyanskayaSLFischerFRCiprianiBBrosnanCF 2001 Developmental plasticity of CNS microglia. Proc Natl Acad Sci U S A 98 6295 6300

28. NewmanTAGaleaIvan RooijenNPerryVH 2005 Blood-derived dendritic cells in an acute brain injury. J Neuroimmunol 166 167 172

29. CavanaghLLWeningerW 2008 Dendritic cell behaviour in vivo: lessons learned from intravital two-photon microscopy. Immunol Cell Biol 86 428 438

30. ButovskyOBukshpanSKunisGJungSSchwartzM 2007 Microglia can be induced by IFN-gamma or IL-4 to express neural or dendritic-like markers. Mol Cell Neurosci 35 490 500

31. PonomarevEDShriverLPMareszKDittelBN 2005 Microglial cell activation and proliferation precedes the onset of CNS autoimmunity. J Neurosci Res 81 374 389

32. RemingtonLTBabcockAAZehntnerSPOwensT 2007 Microglial recruitment, activation, and proliferation in response to primary demyelination. Am J Pathol 170 1713 1724

33. IlarreguiJMRabinovichGA 2010 Tolerogenic dendritic cells in the control of autoimmune neuroinflammation: an emerging role of protein-glycan interactions. Neuroimmunomodulation 17 157 160

34. JainPCoisneCEnzmannGRottapelREngelhardtB 2010 Alpha4beta1 integrin mediates the recruitment of immature dendritic cells across the blood-brain barrier during experimental autoimmune encephalomyelitis. J Immunol 184 7196 7206

35. MaraskovskyEPulendranBBraselKTeepeMRouxER 1997 Dramatic numerical increase of functionally mature dendritic cells in FLT3 ligand-treated mice. Adv Exp Med Biol 417 33 40

36. CavanaghLLBonasioRMazoIBHalinCChengG 2005 Activation of bone marrow-resident memory T cells by circulating, antigen-bearing dendritic cells. Nat Immunol 6 1029 1037

37. DingZXiongKIssekutzTB 2001 Chemokines stimulate human T lymphocyte transendothelial migration to utilize VLA-4 in addition to LFA-1. J Leukoc Biol 69 458 466

38. KinashiTKatagiriK 2005 Regulation of immune cell adhesion and migration by regulator of adhesion and cell polarization enriched in lymphoid tissues. Immunology 116 164 171

39. SchumannKLammermannTBrucknerMLeglerDFPolleuxJ 2010 Immobilized chemokine fields and soluble chemokine gradients cooperatively shape migration patterns of dendritic cells. Immunity 32 703 713

40. ConstantinGMajeedMGiagulliCPiccioLKimJY 2000 Chemokines trigger immediate beta2 integrin affinity and mobility changes: differential regulation and roles in lymphocyte arrest under flow. Immunity 13 759 769

41. WilsonEHWeningerWHunterCA 2010 Trafficking of immune cells in the central nervous system. J Clin Invest 120 1368 1379

42. KarmanJLingCSandorMFabryZ 2004 Initiation of immune responses in brain is promoted by local dendritic cells. J Immunol 173 2353 2361

43. GreterMHeppnerFLLemosMPOdermattBMGoebelsN 2005 Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat Med 11 328 334

44. ZozulyaALOrtlerSLeeJWeidenfellerCSandorM 2009 Intracerebral dendritic cells critically modulate encephalitogenic versus regulatory immune responses in the CNS. J Neurosci 29 140 152

45. ChtanovaTHanSJSchaefferMvan DoorenGGHerzmarkP 2009 Dynamics of T cell, antigen-presenting cell, and pathogen interactions during recall responses in the lymph node. Immunity 31 342 355

46. MelzerTCCranstonHJWeissLMHalonenSK 2010 Host Cell Preference of Toxoplasma gondii Cysts in Murine Brain: A Confocal Study. J Neuroparasitology 1:pii N100505

47. GinhouxFGreterMLeboeufMNandiSSeeP 2010 Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330 841 845

48. GinhouxFGreterMLeboeufMNandiSSeeP 2010 Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330 841 845

49. HessDCAbeTHillWDStuddardAMCarothersJ 2004 Hematopoietic origin of microglial and perivascular cells in brain. Exp Neurol 186 134 144

50. KaurCHaoAJWuCHLingEA 2001 Origin of microglia. Microsc Res Tech 54 2 9

51. ZozulyaALReinkeEBaiuDCKarmanJSandorM 2007 Dendritic cell transmigration through brain microvessel endothelium is regulated by MIP-1alpha chemokine and matrix metalloproteinases. J Immunol 178 520 529

52. PashenkovMTeleshovaNKouwenhovenMKostulasVHuangYM 2002 Elevated expression of CCR5 by myeloid (CD11c+) blood dendritic cells in multiple sclerosis and acute optic neuritis. Clin Exp Immunol 127 519 526

53. KivisakkPMahadDJCallahanMKSikoraKTrebstC 2004 Expression of CCR7 in multiple sclerosis: implications for CNS immunity. Ann Neurol 55 627 638

54. AvilesHStilesJO'DonnellPOrshalJLeidJ 2008 Kinetics of systemic cytokine and brain chemokine gene expression in murine toxoplasma infection. J Parasitol 94 1282 1288

55. StrackAAsensioVCCampbellILSchluterDDeckertM 2002 Chemokines are differentially expressed by astrocytes, microglia and inflammatory leukocytes in Toxoplasma encephalitis and critically regulated by interferon-gamma. Acta Neuropathol 103 458 468

56. GouwyMStruyfSNoppenSSchutyserESpringaelJY 2008 Synergy between coproduced CC and CXC chemokines in monocyte chemotaxis through receptor-mediated events. Mol Pharmacol 74 485 495

57. EngelhardtBKapposL 2008 Natalizumab: targeting alpha4-integrins in multiple sclerosis. Neurodegener Dis 5 16 22

58. YednockTACannonCFritzLCSanchez-MadridFSteinmanL 1992 Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 356 63 66

59. BergerJR 2006 Natalizumab and progressive multifocal leucoencephalopathy. Ann Rheum Dis 65 Suppl 3 iii48 53

60. MolloyESCalabreseLH 2009 Therapy: Targeted but not trouble-free: efalizumab and PML. Nat Rev Rheumatol 5 418 419

61. LindquistRLShakharGDudziakDWardemannHEisenreichT 2004 Visualizing dendritic cell networks in vivo. Nat Immunol 5 1243 1250

62. ChristianNAMiloneMCRankaSSLiGFrailPR 2007 Tat-functionalized near-infrared emissive polymersomes for dendritic cell labeling. Bioconjug Chem 18 31 40

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2011 Číslo 9
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#