Surface Co-Expression of Two Different PfEMP1 Antigens on Single -Infected Erythrocytes Facilitates Binding to ICAM1 and PECAM1

English version České info

The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens play a major role in cytoadhesion of infected erythrocytes (IE), antigenic variation, and immunity to malaria. The current consensus on control of variant surface antigen expression is that only one PfEMP1 encoded by one var gene is expressed per cell at a time. We measured var mRNA transcript levels by real-time Q-PCR, analysed var gene transcripts by single-cell FISH and directly compared these with PfEMP1 antigen surface expression and cytoadhesion in three different antibody-selected P. falciparum 3D7 sub-lines using live confocal microscopy, flow cytometry and in vitro adhesion assays. We found that one selected parasite sub-line simultaneously expressed two different var genes as surface antigens, on single IE. Importantly, and of physiological relevance to adhesion and malaria pathogenesis, this parasite sub-line was found to bind both CD31/PECAM1 and CD54/ICAM1 and to adhere twice as efficiently to human endothelial cells, compared to infected cells having only one PfEMP1 variant on the surface. These new results on PfEMP1 antigen expression indicate that a re-evaluation of the molecular mechanisms involved in P. falciparum adhesion and of the accepted paradigm of absolutely mutually exclusive var gene transcription is required.

Vyšlo v časopise: Surface Co-Expression of Two Different PfEMP1 Antigens on Single -Infected Erythrocytes Facilitates Binding to ICAM1 and PECAM1. PLoS Pathog 6(9): e32767. doi:10.1371/journal.ppat.1001083
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001083

Souhrn

Zdroje

1. MillerLH

GoodMF

MilonG

1994 Malaria pathogenesis. Science 264 1878 1883

2. BarnwellJW

AschAS

NachmanRL

YamayaM

AikawaM

1989 A human 88-kD membrane glycoprotein (CD36) functions in vitro as a receptor for a cytoadherence ligand on Plasmodium falciparum-infected erythrocytes. J Clin Invest 84 765 772

3. BerendtAR

SimmonsDL

TanseyJ

NewboldCI

MarshK

1989 Intercellular adhesion molecule-1 is an endothelial cell adhesion receptor for Plasmodium falciparum. Nature 341 57 59

4. OckenhouseCF

TandonNN

MagowanC

JamiesonGA

ChulayJD

1989 Identification of a platelet membrane glycoprotein as a falciparum malaria sequestration receptor. Science 243 1469 1471

5. TreutigerCJ

HeddiniA

FernandezV

MullerWA

WahlgrenM

1997 PECAM-1/CD31, an endothelial receptor for binding Plasmodium falciparum-infected erythrocytes. Nat Med 3 1405 1408

6. MendisKN

CarterR

1995 Clinical disease and pathogenesis in malaria. Parasitol Today 11 TI1 16

7. HviidL

StaalsoeT

2004 Malaria immunity in infants: a special case of a general phenomenon? Trends Parasitol 20 66 72

8. GardnerMJ

HallN

FungE

WhiteO

BerrimanM

2002 Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419 498 511

9. KyesS

HorrocksP

NewboldC

2001 Antigenic variation at the infected red cell surface in malaria. Annu Rev Microbiol 55 673 707

10. LavstsenT

SalantiA

JensenAT

ArnotDE

TheanderTG

2003 Sub-grouping of Plasmodium falciparum 3D7 var genes based on sequence analysis of coding and non-coding regions. Malar J 2 27

11. KraemerSM

SmithJD

2003 Evidence for the importance of genetic structuring to the structural and functional specialization of the Plasmodium falciparum var gene family. Mol Microbiol 50 1527 1538

12. BiggsBA

GoozeL

WycherleyK

WollishW

SouthwellB

1991 Antigenic variation in Plasmodium falciparum. Proc Natl Acad Sci U S A 88 9171 9174

13. BiggsBA

AndersRF

DillonHE

DavernKM

MartinM

1992 Adherence of infected erythrocytes to venular endothelium selects for antigenic variants of Plasmodium falciparum. J Immunol 149 2047 2054

14. RobertsDJ

CraigAG

BerendtAR

PinchesR

NashG

1992 Rapid switching to multiple antigenic and adhesive phenotypes in malaria. Nature 357 689 692

15. SmithJD

ChitnisCE

CraigAG

RobertsDJ

Hudson-TaylorDE

1995 Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell 82 101 110

16. ChenQ

FernandezV

SundstromA

SchlichtherleM

DattaS

1998 Developmental selection of var gene expression in Plasmodium falciparum. Nature 394 392 395

17. ScherfA

Hernandez-RivasR

BuffetP

BottiusE

BenatarC

1998 Antigenic variation in malaria: in situ switching, relaxed and mutually exclusive transcription of var genes during intra-erythrocytic development in Plasmodium falciparum. EMBO J 17 5418 5426

18. HorrocksP

PinchesR

ChristodoulouZ

KyesS

NewboldC

2004 Variable var transition rates underlie antigenic variation in malaria. Proc Natl Acad Sci USA 101 11129 11134

19. NoviyantiR

BrownGV

WickhamME

DuffyMF

CowmanAF

2001 Multiple var gene transcripts are expressed in Plasmodium falciparum infected erythrocytes selected for adhesion. Mol Biochem Parasitol 114 227 237

20. DuffyMF

BrownGV

BasukiW

KrejanyEO

NoviyantiR

2002 Transcription of multiple var genes by individual, trophozoite-stage Plasmodium falciparum cells expressing a chondroitin sulphate A binding phenotype. Mol Microbiol 43 1285 1293

21. ScherfA

Lopez-RubioJJ

RiviereL

2008 Antigenic variation in Plasmodium falciparum. Annu Rev Microbiol 62 445 470

22. SchieckE

PfahlerJM

SanchezCP

LanzerM

2007 Nuclear run-on analysis of var gene expression in Plasmodium falciparum. Mol Biochem Parasitol 153 207 212

23. KyesS

ChristodoulouZ

PinchesR

KriekN

HorrocksP

2007 Plasmodium falciparum var gene expression is developmentally controlled at the level of RNA polymerase II-mediated transcription initiation. Mol Microbiol 63 1237 1247

24. DeitschKW

CalderwoodMS

WellemsTE

2001 Malaria. Cooperative silencing elements in var genes. Nature 412 875 876

25. CalderwoodMS

Gannoun-ZakiL

WellemsTE

DeitschKW

2003 Plasmodium falciparum var genes are regulated by two regions with separate promoters, one upstream of the coding region and a second within the intron. J Biol Chem 278 34125 34132

26. DzikowskiR

FrankM

DeitschK

2006 Mutually exclusive expression of virulence genes by malaria parasites is regulated independently of antigen production. PLoS Pathog 2 e22

27. VossTS

HealerJ

MartyAJ

DuffyMF

ThompsonJK

2006 A var gene promoter controls allelic exclusion of virulence genes in Plasmodium falciparum malaria. Nature 439 1004 1008

28. DzikowskiR

DeitschKW

2008 Active transcription is required for maintenance of epigenetic memory in the malaria parasite Plasmodium falciparum. J Mol Biol 382 288 297

29. UdomsangpetchR

PipitapornB

SilamutK

PinchesR

KyesS

2002 Febrile temperatures induce cytoadherence of ring-stage Plasmodium falciparum-infected erythrocytes. Proc Natl Acad Sci U S A 99 11825 11829

30. HorrocksP

PinchesRA

ChakravortySJ

PapakrivosJ

ChristodoulouZ

2005 PfEMP1 expression is reduced on the surface of knobless Plasmodium falciparum infected erythrocytes. J Cell Sci 118 2507 2518

31. StaalsoeT

NielsenMA

VestergaardLS

JensenAT

TheanderTG

2003 In vitro selection of Plasmodium falciparum 3D7 for expression of variant surface antigens associated with severe malaria in African children. Parasite Immunol 25 421 427

32. LawrenceMB

SpringerTA

1991 Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell 65 859 873

33. CookeBM

BerendtAR

CraigAG

MacGregorJ

NewboldCI

1994 Rolling and stationary cytoadhesion of red blood cells parasitized by Plasmodium falciparum: separate roles for ICAM-1, CD36 and thrombospondin. Br J Haematol 87 162 170

34. OckenhouseCF

TegoshiT

MaenoY

BenjaminC

HoM

1992 Human vascular endothelial cell adhesion receptors for Plasmodium falciparum-infected erythrocytes: roles for endothelial leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1. J Exp Med 176 1183 1189

35. McCormickCJ

CraigA

RobertsD

NewboldCI

BerendtAR

1997 Intercellular adhesion molecule-1 and CD36 synergize to mediate adherence of Plasmodium falciparum-infected erythrocytes to cultured human microvascular endothelial cells. J Clin Invest 100 2521 2529

36. HeddiniA

PetterssonF

KaiO

ShafiJ

ObieroJ

2001 Fresh isolates from children with severe Plasmodium falciparum malaria bind to multiple receptors. Infect Immun 69 5849 5856

37. ChenQ

HeddiniA

BarraganA

FernandezV

PearceSF

2000 The semiconserved head structure of Plasmodium falciparum erythrocyte membrane protein 1 mediates binding to multiple independent host receptors. J Exp Med 192 1 10

38. BiggsBA

GoozeL

WycherleyK

WilkinsonD

BoydAW

1990 Knob-independent cytoadherence of Plasmodium falciparum to the leukocyte differentiation antigen CD36. J Exp Med 171 1883 1892

39. JensenAT

MagistradoP

SharpS

JoergensenL

LavstsenT

2004 Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes. J Exp Med 199 1179 1190

40. ChamGK

KurtisJ

LusinguJ

TheanderTG

JensenAT

2008 A semi-automated multiplex high-throughput assay for measuring IgG antibodies against Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) domains in small volumes of plasma. Malar J 7 108

41. SalantiA

StaalsoeT

LavstsenT

JensenAT

SowaMP

2003 Selective upregulation of a single distinctly structured var gene in chondroitin sulphate A-adhering Plasmodium falciparum involved in pregnancy-associated malaria. Mol Microbiol 49 179 191

42. DahlbackM

LavstsenT

SalantiA

HviidL

ArnotDE

2007 Changes in var gene mRNA levels during erythrocytic development in two phenotypically distinct Plasmodium falciparum parasites. Malar J 6 78

43. LavstsenT

MagistradoP

HermsenCC

SalantiA

JensenAT

2005 Expression of Plasmodium falciparum erythrocyte membrane protein 1 in experimentally infected humans. Malar J 4 21

44. BerendtAR

McDowallA

CraigAG

BatesPA

SternbergMJ

1992 The binding site on ICAM-1 for Plasmodium falciparum-infected erythrocytes overlaps, but is distinct from, the LFA-1-binding site. Cell 68 71 81

45. RoweJA

MouldsJM

NewboldCI

MillerLH

1997 P. falciparum rosetting mediated by a parasite-variant erythrocyte membrane protein and complement-receptor 1. Nature 388 292 295

46. SmithJD

KyesS

CraigAG

FaganT

Hudson-TaylorD

1998 Analysis of adhesive domains from the A4VAR Plasmodium falciparum erythrocyte membrane protein-1 identifies a CD36 binding domain. Mol Biochem Parasitol 97 133 148

47. MelcherM

MuhleRA

HenrichPP

KraemerSM

AvrilM

2010 Identification of a Role for the PfEMP1 Semi-Conserved Head Structure in Protein Trafficking to the Surface of Plasmodium falciparum Infected Red Blood Cells. Cell Microbiol doi:10.1111/j.1462-5822.2010.01481.x

48. SchieckE

PfahlerJM

SanchezCP

LanzerM

2007 Nuclear run-on analysis of var gene expression in Plasmodium falciparum. Mol Biochem Parasitol 153 207 212

49. AmulicB

SalantiA

LavstsenT

NielsenMA

DeitschKW

2009 An upstream open reading frame controls translation of var2csa, a gene implicated in placental malaria. PLoS Pathog 5 e1000256

50. SanderAF

SalantiA

LavstsenT

NielsenMA

MagistradoP

2009 Multiple var2csa-type PfEMP1 genes located at different chromosomal loci occur in many Plasmodium falciparum isolates. PLoS One 4 e6667

51. BrolinKJ

RibackeU

NilssonS

AnkarklevJ

MollK

2009 Simultaneous transcription of duplicated var2csa gene copies in individual Plasmodium falciparum parasites. Genome Biol 10 R117

52. KupferA

SingerSJ

1988 Molecular dynamics in the membranes of helper T cells. Proc Natl Acad Sci U S A 85 8216 8220

53. UdomsangpetchR

ReinhardtPH

SchollaardtT

ElliottJF

KubesP

1997 Promiscuity of clinical Plasmodium falciparum isolates for multiple adhesion molecules under flow conditions. J Immunol 158 4358 4364

54. McCormickCJ

CraigA

RobertsD

NewboldCI

BerendtAR

55. HoM

HickeyMJ

MurrayAG

AndoneguiG

KubesP

2000 Visualization of Plasmodium falciparum-endothelium interactions in human microvasculature: mimicry of leukocyte recruitment. J Exp Med 192 1205 1211

56. McCormickCJ

CraigA

RobertsD

NewboldCI

BerendtAR

57. RobinsonBA

WelchTL

SmithJD

2003 Widespread functional specialization of Plasmodium falciparum erythrocyte membrane protein 1 family members to bind CD36 analysed across a parasite genome. Mol Microbiol 47 1265 1278

58. ChattopadhyayR

TanejaT

ChakrabartiK

PillaiCR

ChitnisCE

2004 Molecular analysis of the cytoadherence phenotype of a Plasmodium falciparum field isolate that binds intercellular adhesion molecule-1. Mol Biochem Parasitol 133 255 265

59. SpringerAL

SmithLM

MackayDQ

NelsonSO

SmithJD

2004 Functional interdependence of the DBLbeta domain and c2 region for binding of the Plasmodium falciparum variant antigen to ICAM-1. Mol Biochem Parasitol 137 55 64

60. HowellDP

LevinEA

SpringerAL

KraemerSM

PhippardDJ

2008 Mapping a common interaction site used by Plasmodium falciparum Duffy binding-like domains to bind diverse host receptors. Mol Microbiol 67 78 87

61. OleinikovAV

AmosE

FryeIT

RossnagleE

MutabingwaTK

2009 High throughput functional assays of the variant antigen PfEMP1 reveal a single domain in the 3D7 Plasmodium falciparum genome that binds ICAM1 with high affinity and is targeted by naturally acquired neutralizing antibodies. PLoS Pathog 5 e1000386

62. ChenQ

HeddiniA

BarraganA

FernandezV

PearceSF

2000 The semiconserved head structure of Plasmodium falciparum erythrocyte membrane protein 1 mediates binding to multiple independent host receptors. J Exp Med 192 1 10

63. HeddiniA

PetterssonF

KaiO

ShafiJ

ObieroJ

2001 Fresh isolates from children with severe Plasmodium falciparum malaria bind to multiple receptors. Infect Immun 69 5849 5856

64. TurnerGD

MorrisonH

JonesM

DavisTM

LooareesuwanS

1994 An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. Am J Pathol 145 1057 1069

65. TurnerG

1997 Cerebral malaria. Brain Pathol 7 569 582

66. NewboldC

WarnP

BlackG

BerendtA

CraigA

1997 Receptor-specific adhesion and clinical disease in Plasmodium falciparum. Am J Trop Med Hyg 57 389 398

67. Fernandez-ReyesD

CraigAG

KyesSA

PeshuN

SnowRW

1997 A high frequency African coding polymorphism in the N-terminal domain of ICAM-1 predisposing to cerebral malaria in Kenya. Hum Mol Genet 6 1357 1360

68. TreutigerCJ

HeddiniA

FernandezV

MullerWA

WahlgrenM

1997 PECAM-1/CD31, an endothelial receptor for binding Plasmodium falciparum-infected erythrocytes. Nat Med 3 1405 1408

69. LusinguJP

JensenAT

VestergaardLS

MinjaDT

DalgaardMB

2006 Levels of plasma immunoglobulin G with specificity against the cysteine-rich interdomain regions of a semiconserved Plasmodium falciparum erythrocyte membrane protein 1, VAR4, predict protection against malarial anemia and febrile episodes. Infect Immun 74 2867 2875

70. MagistradoPA

LusinguJ

VestergaardLS

LemngeM

LavstsenT

2007 Immunoglobulin G antibody reactivity to a group A Plasmodium falciparum erythrocyte membrane protein 1 and protection from P. falciparum malaria. Infect Immun 75 2415 2420

71. LawrenceMB

SpringerTA

1991 Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell 65 859 873

72. WangCW

HermsenCC

SauerweinRW

ArnotDE

TheanderTG

2009 The Plasmodium falciparum var gene transcription strategy at the onset of blood stage infection in a human volunteer. Parasitol Int

73. DzikowskiR

DeitschKW

2008 Active transcription is required for maintenance of epigenetic memory in the malaria parasite Plasmodium falciparum. J Mol Biol 382 288 297

74. StaalsoeT

GihaHA

DodooD

TheanderTG

HviidL

1999 Detection of antibodies to variant antigens on Plasmodium falciparum-infected erythrocytes by flow cytometry. Cytometry 35 329 336

75. SnounouG

ZhuX

SiripoonN

JarraW

ThaithongS

1999 Biased distribution of msp1 and msp2 allelic variants in Plasmodium falciparum populations in Thailand. Trans R Soc Trop Med Hyg 93 369 374

76. WallikerD

BealeG

1993 Synchronization and cloning of malaria parasites. Methods Mol Biol 21 57 66

77. JoergensenL

TurnerL

MagistradoP

DahlbackMA

VestergaardLS

2006 Limited cross-reactivity among domains of the Plasmodium falciparum clone 3D7 erythrocyte membrane protein 1 family. Infect Immun 74 6778 6784

78. DahlbackM

RaskTS

AndersenPH

NielsenMA

NdamNT

2006 Epitope mapping and topographic analysis of VAR2CSA DBL3X involved in P. falciparum placental sequestration. PLoS Pathog 2 e124

79. BarfodL

NielsenMA

TurnerL

DahlbackM

JensenAT

2006 Baculovirus-expressed constructs induce immunoglobulin G that recognizes VAR2CSA on Plasmodium falciparum-infected erythrocytes. Infect Immun 74 4357 4360

80. SalantiA

DahlbackM

TurnerL

NielsenMA

BarfodL

2004 Evidence for the involvement of VAR2CSA in pregnancy-associated malaria. J Exp Med 200 1197 1203

81. BengtssonD

SowaKM

SalantiA

JensenAT

JoergensenL

2008 A method for visualizing surface-exposed and internal PfEMP1 adhesion antigens in Plasmodium falciparum infected erythrocytes. Malar J 7 101

82. ThompsonJ

2002 In situ detection of RNA in blood- and mosquito-stage malaria parasites. Methods Mol Med 72 225 233

83. PinaudR

MelloCV

VelhoTA

WynneRD

TremereLA

2008 Detection of two mRNA species at single-cell resolution by double-fluorescence in situ hybridization. Nat Protoc 3 1370 1379

84. NielsenMA

ResendeM

AlifrangisM

TurnerL

HviidL

2007 Plasmodium falciparum: VAR2CSA expressed during pregnancy-associated malaria is partially resistant to proteolytic cleavage by trypsin. Exp Parasitol 117 1 8