Parasite-Derived Plasma Microparticles Contribute Significantly to Malaria Infection-Induced Inflammation through Potent Macrophage Stimulation

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There is considerable debate as to the nature of the primary parasite-derived moieties that activate innate pro-inflammatory responses during malaria infection. Microparticles (MPs), which are produced by numerous cell types following vesiculation of the cellular membrane as a consequence of cell death or immune-activation, exert strong pro-inflammatory activity in other disease states. Here we demonstrate that MPs, derived from the plasma of malaria infected mice, but not naive mice, induce potent activation of macrophages in vitro as measured by CD40 up-regulation and TNF production. In vitro, these MPs induced significantly higher levels of macrophage activation than intact infected red blood cells. Immunofluorescence staining revealed that MPs contained significant amounts of parasite material indicating that they are derived primarily from infected red blood cells rather than platelets or endothelial cells. MP driven macrophage activation was completely abolished in the absence of MyD88 and TLR-4 signalling. Similar levels of immunogenic MPs were produced in WT and in TNF^−/−, IFN-γ^−/−, IL-12^−/− and RAG-1^−/− malaria-infected mice, but were not produced in mice injected with LPS, showing that inflammation is not required for the production of MPs during malaria infection. This study therefore establishes parasitized red blood cell-derived MPs as a major inducer of systemic inflammation during malaria infection, raising important questions about their role in severe disease and in the generation of adaptive immune responses.

Vyšlo v časopise: Parasite-Derived Plasma Microparticles Contribute Significantly to Malaria Infection-Induced Inflammation through Potent Macrophage Stimulation. PLoS Pathog 6(1): e32767. doi:10.1371/journal.ppat.1000744
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1000744

Souhrn

Zdroje

1. SnowRW

GuerraCA

NoorAM

MyintHY

HaySI

2005 The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 434 214 217

2. StevensonMM

RileyEM

2004 Innate immunity to malaria. Nat Rev Immunol 4 169 180

3. SchofieldL

GrauGE

2005 Immunological processes in malaria pathogenesis. Nat Rev Immunol 5 722 735

4. GoodMF

XuH

WykesM

EngwerdaCR

2005 Development and regulation of cell-mediated immune responses to the blood stages of malaria: implications for vaccine research. Annu Rev Immunol 23 69 99

5. BaratinM

RoetynckS

LepolardC

FalkC

SawadogoS

2005 Natural killer cell and macrophage cooperation in MyD88-dependent innate responses to Plasmodium falciparum. Proc Natl Acad Sci U S A 102 14747 14752

6. PaisTF

ChatterjeeS

2005 Brain macrophage activation in murine cerebral malaria precedes accumulation of leukocytes and CD8+ T cell proliferation. J Neuroimmunol 163 73 83

7. BalmerP

AlexanderJ

PhillipsRS

2000 Protective immunity to erythrocytic Plasmodium chabaudi AS infection involves IFNgamma-mediated responses and a cellular infiltrate to the liver. Parasitology 121 Pt 5 473 482

8. CouperKN

BlountDG

HafallaJC

van RooijenN

de SouzaJB

2007 Macrophage-mediated but gamma interferon-independent innate immune responses control the primary wave of Plasmodium yoelii parasitemia. Infect Immun 75 5806 5818

9. AdachiK

TsutsuiH

KashiwamuraS

SekiE

NakanoH

2001 Plasmodium berghei infection in mice induces liver injury by an IL-12- and toll-like receptor/myeloid differentiation factor 88-dependent mechanism. J Immunol 167 5928 5934

10. TogbeD

SchofieldL

GrauGE

SchnyderB

BoissayV

2007 Murine cerebral malaria development is independent of toll-like receptor signaling. Am J Pathol 170 1640 1648

11. CobanC

IshiiKJ

UematsuS

ArisueN

SatoS

2007 Pathological role of Toll-like receptor signaling in cerebral malaria. Int Immunol 19 67 79

12. CobanC

IshiiKJ

KawaiT

HemmiH

SatoS

2005 Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin. J Exp Med 201 19 25

13. LepeniesB

CramerJP

BurchardGD

WagnerH

KirschningCJ

2008 Induction of experimental cerebral malaria is independent of TLR2/4/9. Med Microbiol Immunol 197 39 44

14. GriffithJW

O'ConnorC

BernardK

TownT

GoldsteinDR

2007 Toll-like receptor modulation of murine cerebral malaria is dependent on the genetic background of the host. J Infect Dis 196 1553 1564

15. SeixasE

Moura NunesJF

MatosI

CoutinhoA

2009 The interaction between DC and Plasmodium berghei/chabaudi-infected erythrocytes in mice involves direct cell-to-cell contact, internalization and TLR. Eur J Immunol 39 1850 1863

16. CramerJP

LepeniesB

KamenaF

HolscherC

FreudenbergMA

2008 MyD88/IL-18-dependent pathways rather than TLRs control early parasitaemia in non-lethal Plasmodium yoelii infection. Microbes Infect 10 1259 1265

17. FranklinBS

RodriguesSO

AntonelliLR

OliveiraRV

GoncalvesAM

2007 MyD88-dependent activation of dendritic cells and CD4(+) T lymphocytes mediates symptoms, but is not required for the immunological control of parasites during rodent malaria. Microbes Infect 9 881 890

18. FranklinBS

ParrocheP

AtaideMA

LauwF

RopertC

2009 Malaria primes the innate immune response due to interferon-gamma induced enhancement of toll-like receptor expression and function. Proc Natl Acad Sci U S A 106 5789 5794

19. PatelSN

LuZ

AyiK

SerghidesL

GowdaDC

2007 Disruption of CD36 impairs cytokine response to Plasmodium falciparum glycosylphosphatidylinositol and confers susceptibility to severe and fatal malaria in vivo. J Immunol 178 3954 3961

20. KrishnegowdaG

HajjarAM

ZhuJ

DouglassEJ

UematsuS

2005 Induction of proinflammatory responses in macrophages by the glycosylphosphatidylinositols of Plasmodium falciparum: cell signaling receptors, glycosylphosphatidylinositol (GPI) structural requirement, and regulation of GPI activity. J Biol Chem 280 8606 8616

21. UrbanBC

WillcoxN

RobertsDJ

2001 A role for CD36 in the regulation of dendritic cell function. Proc Natl Acad Sci U S A 98 8750 8755

22. NewmanKC

KorbelDS

HafallaJC

RileyEM

2006 Cross-talk with myeloid accessory cells regulates human natural killer cell interferon-gamma responses to malaria. PLoS Pathog 2 e118 doi:10.1371/journal.ppat.0020118

23. PouniotisDS

ProudfootO

BogdanoskaV

ScalzoK

KovacevicS

2005 Selectively impaired CD8+ but not CD4+ T cell cycle arrest during priming as a consequence of dendritic cell interaction with plasmodium-infected red cells. J Immunol 175 3525 3533

24. Ocana-MorgnerC

MotaMM

RodriguezA

2003 Malaria blood stage suppression of liver stage immunity by dendritic cells. J Exp Med 197 143 151

25. UrbanBC

FergusonDJ

PainA

WillcoxN

PlebanskiM

1999 Plasmodium falciparum-infected erythrocytes modulate the maturation of dendritic cells. Nature 400 73 77

26. SeixasE

CrossC

QuinS

LanghorneJ

2001 Direct activation of dendritic cells by the malaria parasite, Plasmodium chabaudi chabaudi. Eur J Immunol 31 2970 2978

27. ParrocheP

LauwFN

GoutagnyN

LatzE

MonksBG

2007 Malaria hemozoin is immunologically inert but radically enhances innate responses by presenting malaria DNA to Toll-like receptor 9. Proc Natl Acad Sci U S A 104 1919 1924

28. MillingtonOR

GibsonVB

RushCM

ZinselmeyerBH

PhillipsRS

2007 Malaria impairs T cell clustering and immune priming despite normal signal 1 from dendritic cells. PLoS Pathog 3 e143 doi:10.1371/journal.ppat.0030143

29. MillingtonOR

Di LorenzoC

PhillipsRS

GarsideP

BrewerJM

2006 Suppression of adaptive immunity to heterologous antigens during Plasmodium infection through hemozoin-induced failure of dendritic cell function. J Biol 5 5

30. KellerCC

YamoO

OumaC

Ong'echaJM

OunahD

2006 Acquisition of hemozoin by monocytes down-regulates interleukin-12 p40 (IL-12p40) transcripts and circulating IL-12p70 through an IL-10-dependent mechanism: in vivo and in vitro findings in severe malarial anemia. Infect Immun 74 5249 5260

31. SchofieldL

HackettF

1993 Signal transduction in host cells by a glycosylphosphatidylinositol toxin of malaria parasites. J Exp Med 177 145 153

32. SchofieldL

HewittMC

EvansK

SiomosMA

SeebergerPH

2002 Synthetic GPI as a candidate anti-toxic vaccine in a model of malaria. Nature 418 785 789

33. CombesV

ColtelN

AlibertM

van EckM

RaymondC

2005 ABCA1 gene deletion protects against cerebral malaria: potential pathogenic role of microparticles in neuropathology. Am J Pathol 166 295 302

34. BurnierL

FontanaP

KwakBR

Angelillo-ScherrerA

2009 Cell-derived microparticles in haemostasis and vascular medicine. Thromb Haemost 101 439 451

35. ColtelN

CombesV

WassmerSC

ChiminiG

GrauGE

2006 Cell vesiculation and immunopathology: implications in cerebral malaria. Microbes Infect 8 2305 2316

36. CombesV

TaylorTE

Juhan-VagueI

MegeJL

MwenechanyaJ

2004 Circulating endothelial microparticles in malawian children with severe falciparum malaria complicated with coma. J American Med Assoc 291 2542 2544

37. TaverneJ

DockrellHM

PlayfairJH

1982 Killing of the malarial parasite Plasmodium yoelii in vitro by cells of myeloid origin. Parasite Immunol 4 77 91

38. ShearHL

NussenzweigRS

BiancoC

1979 Immune phagocytosis in murine malaria. J Exp Med 149 1288 1298

39. PatelSN

SerghidesL

SmithTG

FebbraioM

SilversteinRL

2004 CD36 mediates the phagocytosis of Plasmodium falciparum-infected erythrocytes by rodent macrophages. J Infect Dis 189 204 213

40. CombesV

ColtelN

FailleD

WassmerSC

GrauGE

2006 Cerebral malaria: role of microparticles and platelets in alterations of the blood-brain barrier. Int J Parasitol 36 541 546

41. FailleD

CombesV

MitchellAJ

FontaineA

Juhan-VagueI

2009 Platelet microparticles: a new player in malaria parasite cytoadherence to human brain endothelium. Faseb J

42. WassmerSC

CombesV

CandalFJ

Juhan-VagueI

GrauGE

2006 Platelets potentiate brain endothelial alterations induced by Plasmodium falciparum. Infect Immun 74 645 653

43. HamonY

ChambenoitO

ChiminiG

2002 ABCA1 and the engulfment of apoptotic cells. Biochim Biophys Acta 1585 64 71

44. SalmonBL

OksmanA

GoldbergDE

2001 Malaria parasite exit from the host erythrocyte: a two-step process requiring extraerythrocytic proteolysis. Proc Natl Acad Sci U S A 98 271 276

45. WeinheberN

WolframM

HarbeckeD

AebischerT

1998 Phagocytosis of Leishmania mexicana amastigotes by macrophages leads to a sustained suppression of IL-12 production. Eur J Immunol 28 2467 2477

46. PerryJA

OlverCS

BurnettRC

AveryAC

2005 Cutting edge: the acquisition of TLR tolerance during malaria infection impacts T cell activation. J Immunol 174 5921 5925

47. ZhuJ

KrishnegowdaG

GowdaDC

2005 Induction of proinflammatory responses in macrophages by the glycosylphosphatidylinositols of Plasmodium falciparum: the requirement of extracellular signal-regulated kinase, p38, c-Jun N-terminal kinase and NF-kappaB pathways for the expression of proinflammatory cytokines and nitric oxide. J Biol Chem 280 8617 8627

48. ZhuJ

WuX

GoelS

GowdaNM

KumarS

2009 MAPK-activated protein kinase 2 differentially regulates plasmodium falciparum glycosylphosphatidylinositol-induced production of tumor necrosis factor-{alpha} and interleukin-12 in macrophages. J Biol Chem 284 15750 15761

49. TrinchieriG

SherA

2007 Cooperation of Toll-like receptor signals in innate immune defence. Nat Rev Immunol 7 179 190

50. NapolitaniG

RinaldiA

BertoniF

SallustoF

LanzavecchiaA

2005 Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1-polarizing program in dendritic cells. Nat Immunol 6 769 776

51. MockenhauptFP

CramerJP

HamannL

StegemannMS

EckertJ

2006 Toll-like receptor (TLR) polymorphisms in African children: Common TLR-4 variants predispose to severe malaria. Proc Natl Acad Sci U S A 103 177 182

52. BancroftGJ

CollinsHL

SigolaLB

CrossCE

1994 Modulation of murine macrophage behavior in vivo and in vitro. Methods Cell Biol 45 129 146