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Dynamic Imaging of Experimental Induced Hepatic Granulomas Detects Kupffer Cell-Restricted Antigen Presentation to Antigen-Specific CD8 T Cells


Kupffer cells (KCs) represent the major phagocytic population within the liver and provide an intracellular niche for the survival of a number of important human pathogens. Although KCs have been extensively studied in vitro, little is known of their in vivo response to infection and their capacity to directly interact with antigen-specific CD8+ T cells. Here, using a combination of approaches including whole mount and thin section confocal microscopy, adoptive cell transfer and intra-vital 2-photon microscopy, we demonstrate that KCs represent the only detectable population of mononuclear phagocytes within granulomas induced by Leishmania donovani infection that are capable of presenting parasite-derived peptide to effector CD8+ T cells. This restriction of antigen presentation to KCs within the Leishmania granuloma has important implications for the identification of new candidate vaccine antigens and for the design of novel immuno-therapeutic interventions.


Vyšlo v časopise: Dynamic Imaging of Experimental Induced Hepatic Granulomas Detects Kupffer Cell-Restricted Antigen Presentation to Antigen-Specific CD8 T Cells. PLoS Pathog 6(3): e32767. doi:10.1371/journal.ppat.1000805
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1000805

Souhrn

Kupffer cells (KCs) represent the major phagocytic population within the liver and provide an intracellular niche for the survival of a number of important human pathogens. Although KCs have been extensively studied in vitro, little is known of their in vivo response to infection and their capacity to directly interact with antigen-specific CD8+ T cells. Here, using a combination of approaches including whole mount and thin section confocal microscopy, adoptive cell transfer and intra-vital 2-photon microscopy, we demonstrate that KCs represent the only detectable population of mononuclear phagocytes within granulomas induced by Leishmania donovani infection that are capable of presenting parasite-derived peptide to effector CD8+ T cells. This restriction of antigen presentation to KCs within the Leishmania granuloma has important implications for the identification of new candidate vaccine antigens and for the design of novel immuno-therapeutic interventions.


Zdroje

1. TuijnmanWB

Van WichenDF

SchuurmanHJ

1993 Tissue distribution of human IgG Fc receptors CD16, CD32 and CD64: an immunohistochemical study. APMIS 101 319 329

2. Dominguez-SotoA

Aragoneses-FenollL

Gomez-AguadoF

CorcueraMT

ClariaJ

2009 The pathogen receptor liver and lymph node sinusoidal endotelial cell C-type lectin is expressed in human Kupffer cells and regulated by PU.1. Hepatology 49 287 296

3. SekiE

BrennerDA

2008 Toll-like receptors and adaptor molecules in liver disease: update. Hepatology 48 322 335

4. NaitoM

HasegawaG

EbeY

YamamotoT

2004 Differentiation and function of Kupffer cells. Med Electron Microsc 37 16 28

5. KleinI

CornejoJC

PolakosNK

JohnB

WuenschSA

2007 Kupffer cell heterogeneity: functional properties of bone marrow derived and sessile hepatic macrophages. Blood 110 4077 4085

6. AuffrayC

FoggD

GarfaM

ElainG

Join-LambertO

2007 Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 317 666 670

7. LimmerA

OhlJ

KurtsC

LjunggrenHG

ReissY

2000 Efficient presentation of exogenous antigen by liver endothelial cells to CD8+ T cells results in antigen-specific T-cell tolerance. Nat Med 6 1348 1354

8. BertolinoP

BowenDG

McCaughanGW

Fazekas de St GrothB

2001 Antigen-specific primary activation of CD8+ T cells within the liver. J Immunol 166 5430 5438

9. WinauF

HegasyG

WeiskirchenR

WeberS

CassanC

2007 Ito cells are liver-resident antigen-presenting cells for activating T cell responses. Immunity 26 117 129

10. YoneyamaH

MatsunoK

ZhangY

MuraiM

ItakuraM

2001 Regulation by chemokines of circulating dendritic cell precursors, and the formation of portal tract-associated lymphoid tissue, in a granulomatous liver disease. J Exp Med 193 35 49

11. RussellDG

2007 Who puts the tubercle in tuberculosis? Nat Rev Microbiol 5 39 47

12. GurneyJW

ConcesDJ

1996 Pulmonary histoplasmosis. Radiology 199 297 306

13. BurkeML

JonesMK

GobertGN

LiYS

EllisMK

2009 Immunopathogenesis of human schistosomiasis. Parasite Immunol 31 163 176

14. MurrayHW

2001 Tissue granuloma structure-function in experimental visceral leishmaniasis. Int J Exp Pathol 82 249 267

15. RussellDG

CardonaPJ

KimMJ

AllainS

AltareF

2009 Foamy macrophages and the progression of the human tuberculosis granuloma. Nat Immunol 10 943 948

16. McElrathMJ

MurrayHW

CohnZA

1988 The dynamics of granuloma formation in experimental visceral leishmaniasis. J Exp Med 167 1927 1937

17. CotterellSE

EngwerdaCR

KayePM

1999 Leishmania donovani infection initiates T cell-independent chemokine responses, which are subsequently amplified in a T cell-dependent manner. Eur J Immunol 29 203 214

18. SatoN

KuzielWA

MelbyPC

ReddickRL

KosteckiV

1999 Defects in the generation of IFN-gamma are overcome to control infection with Leishmania donovani in CC chemokine receptor (CCR) 5-, macrophage inflammatory protein-1 alpha-, or CCR2-deficient mice. J Immunol 163 5519 5525

19. EgenJG

RothfuchsAG

FengCG

WinterN

SherA

2008 Macrophage and T cell dynamics during the development and disintegration of mycobacterial granulomas. Immunity 28 271 284

20. MeierCL

SvenssonM

KayePM

2003 Leishmania-induced inhibition of macrophage antigen presentation analyzed at the single-cell level. J Immunol 171 6706 6713

21. OverathP

AebischerT

1999 Antigen presentation by macrophages harboring intravesicular pathogens. Parasitol Today 15 325 332

22. ReinerNE

NgW

McMasterWR

1987 Parasite-accessory cell interactions in murine leishmaniasis. II. Leishmania donovani suppresses macrophage expression of class I and class II major histocompatibility complex gene products. J Immunol 138 1926 1932

23. SternJJ

OcaMJ

RubinBY

AndersonSL

MurrayHW

1988 Role of L3T4+ and LyT-2+ cells in experimental visceral leishmaniasis. J Immunol 140 3971 3977

24. StagerS

SmithDF

KayePM

2000 Immunization with a recombinant stage-regulated surface protein from Leishmania donovani induces protection against visceral leishmaniasis. J Immunol 165 7064 7071

25. PolleyR

StagerS

PrickettS

MaroofA

ZubairiS

2006 Adoptive immunotherapy against experimental visceral leishmaniasis with CD8+ T cells requires the presence of cognate antigen. Infect Immun 74 773 776

26. BasuR

BhaumikS

HaldarAK

NaskarK

DeT

2007 Hybrid cell vaccination resolves Leishmania donovani infection by eliciting a strong CD8+ cytotoxic T-lymphocyte response with concomitant suppression of interleukin-10 (IL-10) but not IL-4 or IL-13. Infect Immun 75 5956 5966

27. Gomes-PereiraS

RodriguesOR

RolaoN

AlmeidaPD

Santos-GomesGM

2004 Hepatic cellular immune responses in mice with “cure” and “non-cure” phenotype to Leishmania infantum infection: importance of CD8+ T cells and TGF-beta production. FEMS Immunol Med Microbiol 41 59 68

28. RosaR

MarquesC

RodriguesOR

Santos-GomesGM

2007 Immunization with Leishmania infantum released proteins confers partial protection against parasite infection with a predominant Th1 specific immune response. Vaccine 25 4525 4532

29. CurryAJ

KayePM

1992 Recombinant interleukin-1 alpha augments granuloma formation and cytokine production but not parasite clearance in mice infected with Leishmania donovani. Infect Immun 60 4422 4426

30. ShanerNC

CampbellRE

SteinbachPA

GiepmansBN

PalmerAE

2004 Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein. Nat Biotechnol 22 1567 1572

31. HumeDA

GordonS

1983 Mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80. Identification of resident macrophages in renal medullary and cortical interstitium and the juxtaglomerular complex. J Exp Med 157 1704 1709

32. MetlayJP

Witmer-PackMD

AggerR

CrowleyMT

LawlessD

1990 The distinct leukocyte integrins of mouse spleen dendritic cells as identified with new hamster monoclonal antibodies. J Exp Med 171 1753 1771

33. KayePM

1987 Inflammatory cells in murine visceral leishmaniasis express a dendritic cell marker. Clin Exp Immunol 70 515 519

34. RacanelliV

RehermannB

2006 The liver as an immunological organ. Hepatology 43 S54 62

35. LloydCM

PhillipsAR

CooperGJ

DunbarPR

2008 Three-colour fluorescence immunohistochemistry reveals the diversity of cells staining for macrophage markers in murine spleen and liver. J Immunol Methods 334 70 81

36. PrickettS

GrayPM

ColpittsSL

ScottP

KayePM

2006 In vivo recognition of ovalbumin expressed by transgenic Leishmania is determined by its subcellular localization. J Immunol 176 4826 4833

37. JoshiT

RodriguezS

PerovicV

CockburnIA

StagerS

2009 B7-H1 blockade increases survival of dysfunctional CD8(+) T cells and confers protection against Leishmania donovani infections. PLoS Pathog 5 e1000431 doi:10.1371/journal.ppat.1000431

38. PorgadorA

YewdellJW

DengY

BenninkJR

GermainRN

1997 Localization, quantitation, and in situ detection of specific peptide-MHC class I complexes using a monoclonal antibody. Immunity 6 715 726

39. GeertsA

NikiT

HellemansK

De CraemerD

Van Den BergK

1998 Purification of rat hepatic stellate cells by side scatter-activated cell sorting. Hepatology 27 590 598

40. CelliS

GarciaZ

BeuneuH

BoussoP

2008 Decoding the dynamics of T cell-dendritic cell interactions in vivo. Immunol Rev 221 182 187

41. BoissonnasA

Scholer-DahireA

FetlerL

AmigorenaS

2009 Multiphoton imaging of cytotoxic T lymphocyte-mediated antitumor immune responses. Curr Top Microbiol Immunol 334 265 287

42. de BoerJ

WilliamsA

SkavdisG

HarkerN

ColesM

2003 Transgenic mice with hematopoietic and lymphoid specific expression of Cre. Eur J Immunol 33 314 325

43. LeiteVH

CroftSL

1996 Hepatic extracellular matrix in BALB/c mice infected with Leishmania donovani. Int J Exp Pathol 77 181 190

44. ZubairiS

SanosSL

HillS

KayePM

2004 Immunotherapy with OX40L-Fc or anti-CTLA-4 enhances local tissue responses and killing of Leishmania donovani. Eur J Immunol 34 1433 1440

45. WeningerW

CrowleyMA

ManjunathN

von AndrianUH

2001 Migratory properties of naive, effector, and memory CD8(+) T cells. J Exp Med 194 953 966

46. MarazuelaM

MorenoA

YebraM

CerezoE

Gomez-GestoC

1991 Hepatic fibrin-ring granulomas: a clinicopathologic study of 23 patients. Hum Pathol 22 607 613

47. MorenoA

MarazuelaM

YebraM

HernandezMJ

HellinT

1988 Hepatic fibrin-ring granulomas in visceral leishmaniasis. Gastroenterology 95 1123 1126

48. SanchezMA

DiazNL

ZerpaO

NegronE

ConvitJ

2004 Organ-specific immunity in canine visceral leishmaniasis: analysis of symptomatic and asymptomatic dogs naturally infected with Leishmania chagasi. Am J Trop Med Hyg 70 618 624

49. EngwerdaCR

AtoM

KayePM

2004 Macrophages, pathology and parasite persistence in experimental visceral leishmaniasis. Trends Parasitol 20 524 530

50. KayePM

SvenssonM

AtoM

MaroofA

PolleyR

2004 The immunopathology of experimental visceral leishmaniasis. Immunol Rev 201 239 253

51. McFarlaneE

PerezC

CharmoyM

AllenbachC

CarterKC

2008 Neutrophils contribute to development of a protective immune response during onset of infection with Leishmania donovani. Infect Immun 76 532 541

52. MorlandB

KaplanG

1977 Macrophage activation in vivo and in vitro. Exp Cell Res 108 279 288

53. EversonMP

ChandlerDB

1992 Changes in distribution, morphology, and tumor necrosis factor-alpha secretion of alveolar macrophage subpopulations during the development of bleomycin-induced pulmonary fibrosis. Am J Pathol 140 503 512

54. RamadoriG

MoriconiF

MalikI

DudasJ

2008 Physiology and pathophysiology of liver inflammation, damage and repair. J Physiol Pharmacol 59 Suppl 1 107 117

55. BilzerM

RoggelF

GerbesAL

2006 Role of Kupffer cells in host defense and liver disease. Liver Int 26 1175 1186

56. StagerS

AlexanderJ

CarterKC

BrombacherF

KayePM

2003 Both interleukin-4 (IL-4) and IL-4 receptor alpha signaling contribute to the development of hepatic granulomas with optimal antileishmanial activity. Infect Immun 71 4804 4807

57. FluggeAJ

TimmisJ

AndrewsP

MooreJ

KayePM

2009 Modelling and Simulation of Granuloma Formation in Visceral Leishmaniasis. CEC In Press

58. YoungD

StarkJ

KirschnerD

2008 Systems biology of persistent infection: tuberculosis as a case study. Nat Rev Microbiol 6 520 528

59. De TrezC

MagezS

AkiraS

RyffelB

CarlierY

2009 iNOS-producing inflammatory dendritic cells constitute the major infected cell type during the chronic Leishmania major infection phase of C57BL/6 resistant mice. PLoS Pathog 5 e1000494 doi:10.1371/journal.ppat.1000494

60. LeonB

Lopez-BravoM

ArdavinC

2007 Monocyte-derived dendritic cells formed at the infection site control the induction of protective T helper 1 responses against Leishmania. Immunity 26 519 531

61. DaviesEV

SingletonAM

BlackwellJM

1988 Differences in Lsh gene control over systemic Leishmania major and Leishmania donovani or Leishmania mexicana mexicana infections are caused by differential targeting to infiltrating and resident liver macrophage populations. Infect Immun 56 1128 1134

62. CarlinLM

ElemeK

McCannFE

DavisDM

2001 Intercellular transfer and supramolecular organization of human leukocyte antigen C at inhibitory natural killer cell immune synapses. J Exp Med 194 1507 1517

63. HuangJF

YangY

SepulvedaH

ShiW

HwangI

1999 TCR-Mediated internalization of peptide-MHC complexes acquired by T cells. Science 286 952 954

64. PrinciottaMF

FinziD

QianSB

GibbsJ

SchuchmannS

2003 Quantitating protein synthesis, degradation, and endogenous antigen processing. Immunity 18 343 354

65. SykulevY

JooM

VturinaI

TsomidesTJ

EisenHN

1996 Evidence that a single peptide-MHC complex on a target cell can elicit a cytolytic T cell response. Immunity 4 565 571

66. ChtanovaT

HanSJ

SchaefferM

van DoorenGG

HerzmarkP

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

67. JohnB

HarrisTH

TaitED

WilsonEH

GreggB

2009 Dynamic Imaging of CD8(+) T cells and dendritic cells during infection with Toxoplasma gondii. PLoS Pathog 5 e1000505 doi:10.1371/journal.ppat.1000505

68. BoissonnasA

FetlerL

ZeelenbergIS

HuguesS

AmigorenaS

2007 In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor. J Exp Med 204 345 356

69. MrassP

TakanoH

NgLG

DaxiniS

LasaroMO

2006 Random migration precedes stable target cell interactions of tumor-infiltrating T cells. J Exp Med 203 2749 2761

70. SchaefferM

HanSJ

ChtanovaT

van DoorenGG

HerzmarkP

2009 Dynamic imaging of T cell-parasite interactions in the brains of mice chronically infected with Toxoplasma gondii. J Immunol 182 6379 6393

71. WilsonEH

HarrisTH

MrassP

JohnB

TaitED

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

72. MempelTR

PittetMJ

KhazaieK

WeningerW

WeisslederR

2006 Regulatory T cells reversibly suppress cytotoxic T cell function independent of effector differentiation. Immunity 25 129 141

73. BreartB

LemaitreF

CelliS

BoussoP

2008 Two-photon imaging of intratumoral CD8+ T cell cytotoxic activity during adoptive T cell therapy in mice. J Clin Invest 118 1390 1397

74. WuF

WuenschSA

AzadnivM

EbrahimkhaniMR

CrispeIN

2009 Galactosylated LDL Nanoparticles: A Novel Targeting Delivery System To Deliver Antigen to Macrophages and Enhance Antigen Specific T Cell Responses. Mol Pharm

75. YouQ

ChengL

KedlRM

JuC

2008 Mechanism of T cell tolerance induction by murine hepatic Kupffer cells. Hepatology 48 978 990

76. MisslitzA

MottramJC

OverathP

AebischerT

2000 Targeted integration into a rRNA locus results in uniform and high level expression of transgenes in Leishmania amastigotes. Mol Biochem Parasitol 107 251 261

77. Veiga-FernandesH

ColesMC

FosterKE

PatelA

WilliamsA

2007 Tyrosine kinase receptor RET is a key regulator of Peyer's patch organogenesis. Nature 446 547 551

78. StanleyAC

ZhouY

AmanteFH

RandallLM

HaqueA

2008 Activation of invariant NKT cells exacerbates experimental visceral leishmaniasis. PLoS Pathog 4 e1000028 doi:10.1371/journal.ppat.1000028

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