#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Immune Evasion by : Differential Targeting of Dendritic Cell Subpopulations


CD4+ T cells are essential for the control of Yersinia enterocolitica (Ye) infection in mice. Ye can inhibit dendritic cell (DC) antigen uptake and degradation, maturation and subsequently T-cell activation in vitro. Here we investigated the effects of Ye infection on splenic DCs and T-cell proliferation in an experimental mouse infection model. We found that OVA-specific CD4+ T cells had a reduced potential to proliferate when stimulated with OVA after infection with Ye compared to control mice. Additionally, proliferation of OVA-specific CD4+ T cells was markedly reduced when cultured with splenic CD8α+ DCs from Ye infected mice in the presence of OVA. In contrast, T-cell proliferation was not impaired in cultures with CD4+ or CD4CD8α DCs isolated from Ye infected mice. However, OVA uptake and degradation as well as cytokine production were impaired in CD8α+ DCs, but not in CD4+ and CD4CD8α DCs after Ye infection. Pathogenicity factors (Yops) from Ye were most frequently injected into CD8α+ DCs, resulting in less MHC class II and CD86 expression than on non-injected CD8α+ DCs. Three days post infection with Ye the number of splenic CD8α+ and CD4+ DCs was reduced by 50% and 90%, respectively. The decreased number of DC subsets, which was dependent on TLR4 and TRIF signaling, was the result of a faster proliferation and suppressed de novo DC generation. Together, we show that Ye infection negatively regulates the stimulatory capacity of some but not all splenic DC subpopulations in vivo. This leads to differential antigen uptake and degradation, cytokine production, cell loss, and cell death rates in various DC subpopulations. The data suggest that these effects might be caused directly by injection of Yops into DCs and indirectly by affecting the homeostasis of CD4+ and CD8α+ DCs. These events may contribute to reduced T-cell proliferation and immune evasion of Ye.


Vyšlo v časopise: Immune Evasion by : Differential Targeting of Dendritic Cell Subpopulations. PLoS Pathog 6(11): e32767. doi:10.1371/journal.ppat.1001212
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001212

Souhrn

CD4+ T cells are essential for the control of Yersinia enterocolitica (Ye) infection in mice. Ye can inhibit dendritic cell (DC) antigen uptake and degradation, maturation and subsequently T-cell activation in vitro. Here we investigated the effects of Ye infection on splenic DCs and T-cell proliferation in an experimental mouse infection model. We found that OVA-specific CD4+ T cells had a reduced potential to proliferate when stimulated with OVA after infection with Ye compared to control mice. Additionally, proliferation of OVA-specific CD4+ T cells was markedly reduced when cultured with splenic CD8α+ DCs from Ye infected mice in the presence of OVA. In contrast, T-cell proliferation was not impaired in cultures with CD4+ or CD4CD8α DCs isolated from Ye infected mice. However, OVA uptake and degradation as well as cytokine production were impaired in CD8α+ DCs, but not in CD4+ and CD4CD8α DCs after Ye infection. Pathogenicity factors (Yops) from Ye were most frequently injected into CD8α+ DCs, resulting in less MHC class II and CD86 expression than on non-injected CD8α+ DCs. Three days post infection with Ye the number of splenic CD8α+ and CD4+ DCs was reduced by 50% and 90%, respectively. The decreased number of DC subsets, which was dependent on TLR4 and TRIF signaling, was the result of a faster proliferation and suppressed de novo DC generation. Together, we show that Ye infection negatively regulates the stimulatory capacity of some but not all splenic DC subpopulations in vivo. This leads to differential antigen uptake and degradation, cytokine production, cell loss, and cell death rates in various DC subpopulations. The data suggest that these effects might be caused directly by injection of Yops into DCs and indirectly by affecting the homeostasis of CD4+ and CD8α+ DCs. These events may contribute to reduced T-cell proliferation and immune evasion of Ye.


Zdroje

1. FearonDT

LocksleyRM

1996

The instructive role of innate immunity in the acquired immune response.

Science

272

50

53

2. HoffmannJA

KafatosFC

JanewayCA

EzekowitzRA

1999

Phylogenetic perspectives in innate immunity.

Science

284

1313

1318

3. MedzhitovR

JanewayCAJr

1997

Innate immunity: impact on the adaptive immune response.

Curr Opin Immunol

9

4

9

4. MatzingerP

1994

Tolerance, danger, and the extended family.

Annu Rev Immunol

12

991

1045

5. MuzioM

NatoliG

SaccaniS

LevreroM

MantovaniA

1998

The human toll signaling pathway: divergence of nuclear factor kappaB and JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6).

J Exp Med

187

2097

2101

6. BrightbillHD

LibratyDH

KrutzikSR

YangRB

BelisleJT

1999

Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors.

Science

285

732

736

7. AliprantisAO

YangRB

MarkMR

SuggettS

DevauxB

1999

Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2.

Science

285

736

739

8. BanchereauJ

SteinmanRM

1998

Dendritic cells and the control of immunity.

Nature

392

245

252

9. BellD

YoungJW

BanchereauJ

1999

Dendritic cells.

Adv Immunol

72

255

324

10. HartDN

1997

Dendritic cells: unique leukocyte populations which control the primary immune response.

Blood

90

3245

3287

11. SteinmanRM

1991

The dendritic cell system and its role in immunogenicity.

Annu Rev Immunol

9

271

296

12. BanchereauJ

BriereF

CauxC

DavoustJ

LebecqueS

2000

Immunobiology of dendritic cells.

Annu Rev Immunol

18

767

811

13. IwasakiA

MedzhitovR

2004

Toll-like receptor control of the adaptive immune responses.

Nat Immunol

5

987

995

14. VremecD

PooleyJ

HochreinH

WuL

ShortmanK

2000

CD4 and CD8 expression by dendritic cell subtypes in mouse thymus and spleen.

J Immunol

164

2978

2986

15. De SmedtT

PajakB

MurailleE

LespagnardL

HeinenE

1996

Regulation of dendritic cell numbers and maturation by lipopolysaccharide in vivo.

J Exp Med

184

1413

1424

16. De SmedtT

PajakB

KlausGG

NoelleRJ

UrbainJ

1998

Antigen-specific T lymphocytes regulate lipopolysaccharide-induced apoptosis of dendritic cells in vivo.

J Immunol

161

4476

4479

17. IdoyagaJ

SudaN

SudaK

ParkCG

SteinmanRM

2009

Antibody to Langerin/CD207 localizes large numbers of CD8alpha+ dendritic cells to the marginal zone of mouse spleen.

Proc Natl Acad Sci U S A

106

1524

1529

18. Maldonado-LopezR

De SmedtT

MichelP

GodfroidJ

PajakB

1999

CD8alpha+ and CD8alpha- subclasses of dendritic cells direct the development of distinct T helper cells in vivo.

J Exp Med

189

587

592

19. SchnorrerP

BehrensGM

WilsonNS

PooleyJL

SmithCM

2006

The dominant role of CD8+ dendritic cells in cross-presentation is not dictated by antigen capture.

Proc Natl Acad Sci U S A

103

10729

10734

20. PooleyJL

HeathWR

ShortmanK

2001

Cutting edge: intravenous soluble antigen is presented to CD4 T cells by CD8- dendritic cells, but cross-presented to CD8 T cells by CD8+ dendritic cells.

J Immunol

166

5327

5330

21. CoverTL

AberRC

1989

Yersinia enterocolitica.

N Engl J Med

321

16

24

22. CornelisGR

2002

Yersinia type III secretion: send in the effectors.

J Cell Biol

158

401

408

23. AiliM

TelepnevM

HallbergB

Wolf-WatzH

RosqvistR

2003

In vitro GAP activity towards RhoA, Rac1 and Cdc42 is not a prerequisite for YopE induced HeLa cell cytotoxicity.

Microb Pathog

34

297

308

24. BarzC

AbahjiTN

TrulzschK

HeesemannJ

2000

The Yersinia Ser/Thr protein kinase YpkA/YopO directly interacts with the small GTPases RhoA and Rac-1.

FEBS Lett

482

139

143

25. BlackDS

BliskaJB

1997

Identification of p130Cas as a substrate of Yersinia YopH (Yop51), a bacterial protein tyrosine phosphatase that translocates into mammalian cells and targets focal adhesions.

EMBO J

16

2730

2744

26. IriarteM

CornelisGR

1998

YopT, a new Yersinia Yop effector protein, affects the cytoskeleton of host cells.

Mol Microbiol

29

915

929

27. ErfurthSE

GrobnerS

KramerU

GunstDS

SoldanovaI

2004

Yersinia enterocolitica induces apoptosis and inhibits surface molecule expression and cytokine production in murine dendritic cells.

Infect Immun

72

7045

7054

28. OrthK

PalmerLE

BaoZQ

StewartS

RudolphAE

1999

Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector.

Science

285

1920

1923

29. PalmerLE

HobbieS

GalanJE

BliskaJB

1998

YopJ of Yersinia pseudotuberculosis is required for the inhibition of macrophage TNF-alpha production and downregulation of the MAP kinases p38 and JNK.

Mol Microbiol

27

953

965

30. RuckdeschelK

RoggenkampA

LafontV

MangeatP

HeesemannJ

1997

Interaction of Yersinia enterocolitica with macrophages leads to macrophage cell death through apoptosis.

Infect Immun

65

4813

4821

31. AdkinsI

SchulzS

BorgmannS

AutenriethIB

GrobnerS

2008

Differential roles of Yersinia outer protein P-mediated inhibition of nuclear factor-kappa B in the induction of cell death in dendritic cells and macrophages.

J Med Microbiol

57

139

144

32. GrobnerS

AdkinsI

SchulzS

RichterK

BorgmannS

2007

Catalytically active Yersinia outer protein P induces cleavage of RIP and caspase-8 at the level of the DISC independently of death receptors in dendritic cells.

Apoptosis

12

1813

1825

33. GrobnerS

AutenriethSE

SoldanovaI

GunstDS

SchallerM

2006

Yersinia YopP-induced apoptotic cell death in murine dendritic cells is partially independent from action of caspases and exhibits necrosis-like features.

Apoptosis

11

1959

1968

34. AutenriethIB

TingleA

Reske-KunzA

HeesemannJ

1992

T lymphocytes mediate protection against Yersinia enterocolitica in mice: characterization of murine T-cell clones specific for Y. enterocolitica.

Infect Immun

60

1140

1149

35. AutenriethIB

HantschmannP

HeymerB

HeesemannJ

1993

Immunohistological characterization of the cellular immune response against Yersinia enterocolitica in mice: evidence for the involvement of T lymphocytes.

Immunobiology

187

1

16

36. BohnE

HeesemannJ

EhlersS

AutenriethIB

1994

Early gamma interferon mRNA expression is associated with resistance of mice against Yersinia enterocolitica.

Infect Immun

62

3027

3032

37. BohnE

AutenriethIB

1996

IL-12 is essential for resistance against Yersinia enterocolitica by triggering IFN-gamma production in NK cells and CD4+ T cells.

J Immunol

156

1458

1468

38. BohnE

SingA

ZumbihlR

BielfeldtC

OkamuraH

1998

IL-18 (IFN-gamma-inducing factor) regulates early cytokine production in, and promotes resolution of, bacterial infection in mice.

J Immunol

160

299

307

39. AutenriethIB

HeesemannJ

1992

In vivo neutralization of tumor necrosis factor-alpha and interferon-gamma abrogates resistance to Yersinia enterocolitica infection in mice.

Med Microbiol Immunol

181

333

338

40. AutenriethSE

SoldanovaI

RosemannR

GunstD

ZahirN

2007

Yersinia enterocolitica YopP inhibits MAP kinase-mediated antigen uptake in dendritic cells.

Cell Microbiol

9

425

437

41. AdkinsI

KoberleM

GrobnerS

AutenriethSE

BohnE

2008

Y. enterocolitica inhibits antigen degradation in dendritic cells.

Microbes Infect

10

798

806

42. TrulzschK

SporlederT

IgweEI

RussmannH

HeesemannJ

2004

Contribution of the major secreted yops of Yersinia enterocolitica O:8 to pathogenicity in the mouse infection model.

Infect Immun

72

5227

5234

43. BarndenMJ

AllisonJ

HeathWR

CarboneFR

1998

Defective TCR expression in transgenic mice constructed using cDNA-based alpha- and beta-chain genes under the control of heterologous regulatory elements.

Immunol Cell Biol

76

34

40

44. CornelisGR

2002

The Yersinia Ysc-Yop ‘type III’ weaponry.

Nat Rev Mol Cell Biol

3

742

752

45. MarketonMM

DePaoloRW

DeBordKL

JabriB

SchneewindO

2005

Plague bacteria target immune cells during infection.

Science

309

1739

1741

46. KoberleM

Klein-GuntherA

SchutzM

FritzM

BerchtoldS

2009

Yersinia enterocolitica targets cells of the innate and adaptive immune system by injection of Yops in a mouse infection model.

PLoS Pathog

5

e1000551

47. DurandEA

Maldonado-ArochoFJ

CastilloC

WalshRL

MecsasJ

2010

The presence of professional phagocytes dictates the number of host cells targeted for Yop translocation during infection.

Cell Microbiol

48. CharpentierX

OswaldE

2004

Identification of the secretion and translocation domain of the enteropathogenic and enterohemorrhagic Escherichia coli effector Cif, using TEM-1 beta-lactamase as a new fluorescence-based reporter.

J Bacteriol

186

5486

5495

49. GeddesK

CruzF

HeffronF

2007

Analysis of cells targeted by Salmonella type III secretion in vivo.

PLoS Pathog

3

e196

50. ZlokarnikG

NegulescuPA

KnappTE

MereL

BurresN

1998

Quantitation of transcription and clonal selection of single living cells with beta-lactamase as reporter.

Science

279

84

88

51. De TrezC

PajakB

BraitM

GlaichenhausN

UrbainJ

2005

TLR4 and Toll-IL-1 receptor domain-containing adapter-inducing IFN-beta, but not MyD88, regulate Escherichia coli-induced dendritic cell maturation and apoptosis in vivo.

J Immunol

175

839

846

52. KamathAT

PooleyJ

O'KeeffeMA

VremecD

ZhanY

2000

The development, maturation, and turnover rate of mouse spleen dendritic cell populations.

J Immunol

165

6762

6770

53. KamathAT

HenriS

BattyeF

ToughDF

ShortmanK

2002

Developmental kinetics and lifespan of dendritic cells in mouse lymphoid organs.

Blood

100

1734

1741

54. GeissmannF

ManzMG

JungS

SiewekeMH

MeradM

2010

Development of monocytes, macrophages, and dendritic cells.

Science

327

656

661

55. LiuK

WaskowC

LiuX

YaoK

HohJ

2007

Origin of dendritic cells in peripheral lymphoid organs of mice.

Nat Immunol

8

578

583

56. HochwellerK

StrieglerJ

HammerlingGJ

GarbiN

2008

A novel CD11c.DTR transgenic mouse for depletion of dendritic cells reveals their requirement for homeostatic proliferation of natural killer cells.

Eur J Immunol

38

2776

2783

57. PulendranB

SmithJL

CasparyG

BraselK

PettitD

1999

Distinct dendritic cell subsets differentially regulate the class of immune response in vivo.

Proc Natl Acad Sci U S A

96

1036

1041

58. Maldonado-LopezR

De SmedtT

PajakB

HeirmanC

ThielemansK

1999

Role of CD8alpha+ and CD8alpha- dendritic cells in the induction of primary immune responses in vivo.

J Leukoc Biol

66

242

246

59. Maldonado-LopezR

MaliszewskiC

UrbainJ

MoserM

2001

Cytokines regulate the capacity of CD8alpha(+) and CD8alpha(-) dendritic cells to prime Th1/Th2 cells in vivo.

J Immunol

167

4345

4350

60. DalodM

Salazar-MatherTP

MalmgaardL

LewisC

Asselin-PaturelC

2002

Interferon alpha/beta and interleukin 12 responses to viral infections: pathways regulating dendritic cell cytokine expression in vivo.

J Exp Med

195

517

528

61. MaroofA

KayePM

2008

Temporal regulation of interleukin-12p70 (IL-12p70) and IL-12-related cytokines in splenic dendritic cell subsets during Leishmania donovani infection.

Infect Immun

76

239

249

62. YrlidU

WickMJ

2002

Antigen presentation capacity and cytokine production by murine splenic dendritic cell subsets upon Salmonella encounter.

J Immunol

169

108

116

63. Reis eSousa

HienyS

Scharton-KerstenT

JankovicD

CharestH

1997

In vivo microbial stimulation induces rapid CD40 ligand-independent production of interleukin 12 by dendritic cells and their redistribution to T cell areas.

J Exp Med

186

1819

1829

64. EdwardsAD

DieboldSS

SlackEM

TomizawaH

HemmiH

2003

Toll-like receptor expression in murine DC subsets: lack of TLR7 expression by CD8 alpha+ DC correlates with unresponsiveness to imidazoquinolines.

Eur J Immunol

33

827

833

65. GarrettWS

ChenLM

KroschewskiR

EbersoldM

TurleyS

2000

Developmental control of endocytosis in dendritic cells by Cdc42.

Cell

102

325

334

66. SteinmanRM

SwansonJ

1995

The endocytic activity of dendritic cells.

J Exp Med

182

283

288

67. WestMA

PrescottAR

EskelinenEL

RidleyAJ

WattsC

2000

Rac is required for constitutive macropinocytosis by dendritic cells but does not control its downregulation.

Curr Biol

10

839

848

68. BurgdorfS

Lukacs-KornekV

KurtsC

2006

The mannose receptor mediates uptake of soluble but not of cell-associated antigen for cross-presentation.

J Immunol

176

6770

6776

69. BurgdorfS

KautzA

BohnertV

KnollePA

KurtsC

2007

Distinct pathways of antigen uptake and intracellular routing in CD4 and CD8 T cell activation.

Science

316

612

616

70. SponaasAM

CadmanET

VoisineC

HarrisonV

BoonstraA

2006

Malaria infection changes the ability of splenic dendritic cell populations to stimulate antigen-specific T cells.

J Exp Med

203

1427

1433

71. SundquistM

WickMJ

2005

TNF-alpha-dependent and -independent maturation of dendritic cells and recruited CD11c(int)CD11b+ Cells during oral Salmonella infection.

J Immunol

175

3287

3298

72. TamMA

WickMJ

2006

Differential expansion, activation and effector functions of conventional and plasmacytoid dendritic cells in mouse tissues transiently infected with Listeria monocytogenes.

Cell Microbiol

8

1172

1187

73. TamMA

SundquistM

WickMJ

2008

MyD88 and IFN-alphabeta differentially control maturation of bystander but not Salmonella-associated dendritic cells or CD11cintCD11b+ cells during infection.

Cell Microbiol

10

1517

1529

74. YaoT

MecsasJ

HealyJI

FalkowS

ChienY

1999

Suppression of T and B lymphocyte activation by a Yersinia pseudotuberculosis virulence factor, yopH.

J Exp Med

190

1343

1350

75. GerkeC

FalkowS

ChienYH

2005

The adaptor molecules LAT and SLP-76 are specifically targeted by Yersinia to inhibit T cell activation.

J Exp Med

201

361

371

76. MatteiF

BracciL

ToughDF

BelardelliF

SchiavoniG

2009

Type I IFN regulate DC turnover in vivo.

Eur J Immunol

39

1807

1818

77. SundquistM

WickMJ

2009

Salmonella induces death of CD8{alpha}+ dendritic cells but not CD11cintCD11b+ inflammatory cells in vivo via MyD88 and TNFR1.

J Leukoc Biol

85

225

234

78. BergsbakenT

CooksonBT

2007

Macrophage activation redirects yersinia-infected host cell death from apoptosis to caspase-1-dependent pyroptosis.

PLoS Pathog

3

e161

79. HochwellerK

MiloudT

StrieglerJ

NaikS

HammerlingGJ

2009

Homeostasis of dendritic cells in lymphoid organs is controlled by regulation of their precursors via a feedback loop.

Blood

114

4411

4421

80. JiaT

SerbinaNV

BrandlK

ZhongMX

LeinerIM

2008

Additive roles for MCP-1 and MCP-3 in CCR2-mediated recruitment of inflammatory monocytes during Listeria monocytogenes infection.

J Immunol

180

6846

6853

81. SerbinaNV

Salazar-MatherTP

BironCA

KuzielWA

PamerEG

2003

TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection.

Immunity

19

59

70

82. 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

83. NeuenhahnM

KerksiekKM

NauerthM

SuhreMH

SchiemannM

2006

CD8alpha+ dendritic cells are required for efficient entry of Listeria monocytogenes into the spleen.

Immunity

25

619

630

84. HoebeK

DuX

GeorgelP

JanssenE

TabetaK

2003

Identification of Lps2 as a key transducer of MyD88-independent TIR signalling.

Nature

424

743

748

85. HemmiH

KaishoT

TakeuchiO

SatoS

SanjoH

2002

Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway.

Nat Immunol

3

196

200

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2010 Číslo 11
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

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#