T Cell-Dependence of Lassa Fever Pathogenesis

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Lassa virus (LASV), the causative agent of Lassa fever (LF), is endemic in West Africa, accounting for substantial morbidity and mortality. In spite of ongoing research efforts, LF pathogenesis and mechanisms of LASV immune control remain poorly understood. While normal laboratory mice are resistant to LASV, we report that mice expressing humanized instead of murine MHC class I (MHC-I) failed to control LASV infection and develop severe LF. Infection of MHC-I knockout mice confirmed a key role for MHC-I-restricted T cell responses in controlling LASV. Intriguingly we found that T cell depletion in LASV-infected HHD mice prevented disease, irrespective of high-level viremia. Widespread activation of monocyte/macrophage lineage cells, manifest through inducible NO synthase expression, and elevated IL-12p40 serum levels indicated a systemic inflammatory condition. The absence of extensive monocyte/macrophage activation in T cell-depleted mice suggested that T cell responses contribute to deleterious innate inflammatory reactions and LF pathogenesis. Our observations in mice indicate a dual role for T cells, not only protecting from LASV, but also enhancing LF pathogenesis. The possibility of T cell-driven enhancement and immunopathogenesis should be given consideration in future LF vaccine development.

Vyšlo v časopise: T Cell-Dependence of Lassa Fever Pathogenesis. PLoS Pathog 6(3): e32767. doi:10.1371/journal.ppat.1000836
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1000836

Souhrn

Zdroje

1. BuckleySM

CasalsJ

DownsWG

1970 Isolation and antigenic characterization of Lassa virus. Nature 227 174

2. McCormickJB

WebbPA

KrebsJW

JohnsonKM

SmithES

1987 A prospective study of the epidemiology and ecology of Lassa fever. J Infect Dis 155 437 444

3. HaasWH

BreuerT

PfaffG

SchmitzH

KohlerP

2003 Imported Lassa fever in Germany: surveillance and management of contact persons. Clin Infect Dis 36 1254 1258

4. BorioL

InglesbyT

PetersCJ

SchmaljohnAL

HughesJM

2002 Hemorrhagic fever viruses as biological weapons: medical and public health management. Jama 287 2391 2405

5. CharrelRN

de LamballerieX

2003 Arenaviruses other than Lassa virus. Antiviral Res 57 89 100

6. GeisbertTW

JahrlingPB

2004 Exotic emerging viral diseases: progress and challenges. Nat Med 10 S110 121

7. GuntherS

LenzO

2004 Lassa virus. Crit Rev Clin Lab Sci 41 339 390

8. HalsteadSB

O'RourkeEJ

1977 Antibody-enhanced dengue virus infection in primate leukocytes. Nature 265 739 741

9. HalsteadSB

1979 In vivo enhancement of dengue virus infection in rhesus monkeys by passively transferred antibody. J Infect Dis 140 527 533

10. MongkolsapayaJ

DejnirattisaiW

XuXN

VasanawathanaS

TangthawornchaikulN

2003 Original antigenic sin and apopotosis in the pathogenesis of dengue hemorrhagic fever. Nat Med 9 921 927

11. LokeH

BethellDB

PhuongCX

DungM

SchneiderJ

2001 Strong HLA class I--restricted T cell responses in dengue hemorrhagic fever: a double-edged sword? J Infect Dis 184 1369 1373

12. LanNT

KikuchiM

HuongVT

Ha doQ

ThuyTT

2008 Protective and Enhancing HLA Alleles, HLA-DRB1*0901 and HLA-A*24, for Severe Forms of Dengue Virus Infection, Dengue Hemorrhagic Fever and Dengue Shock Syndrome. PLoS Negl Trop Dis 2 e304 doi:10.1371/journal.pntd.0000304

13. ChenYC

WangSY

2002 Activation of terminally differentiated human monocytes/macrophages by dengue virus: productive infection, hierarchical production of innate cytokines and chemokines, and the synergistic effect of lipopolysaccharide. J Virol 76 9877 9887

14. ChenST

LinYL

HuangMT

WuMF

ChengSC

2008 CLEC5A is critical for dengue-virus-induced lethal disease. Nature 453 672 676

15. HatchS

MathewA

RothmanA

2008 Dengue vaccine: opportunities and challenges. IDrugs 11 42 45

16. KimHW

CancholaJG

BrandtCD

PylesG

ChanockRM

1969 Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Am J Epidemiol 89 422 434

17. FulginitiVA

EllerJJ

DownieAW

KempeCH

1967 Altered reactivity to measles virus. Atypical measles in children previously immunized with inactivated measles virus vaccines. JAMA 202 1075 1080

18. OpenshawPJ

TregoningJS

2005 Immune responses and disease enhancement during respiratory syncytial virus infection. Clin Microbiol Rev 18 541 555

19. MahantyS

BauschDG

ThomasRL

GobaA

BahA

2001 Low levels of interleukin-8 and interferon-inducible protein-10 in serum are associated with fatal infections in acute Lassa fever. J Infect Dis 183 1713 1721

20. ter MeulenJ

SakhoM

KoulemouK

MagassoubaN

BahA

2004 Activation of the cytokine network and unfavorable outcome in patients with yellow fever. J Infect Dis 190 1821 1827

21. LukashevichIS

TikhonovI

RodasJD

ZapataJC

YangY

2003 Arenavirus-mediated liver pathology: acute lymphocytic choriomeningitis virus infection of rhesus macaques is characterized by high-level interleukin-6 expression and hepatocyte proliferation. J Virol 77 1727 1737

22. SchmitzH

KohlerB

LaueT

DrostenC

VeldkampPJ

2002 Monitoring of clinical and laboratory data in two cases of imported Lassa fever. Microbes Infect 4 43 50

23. GeisbertTW

HensleyLE

LarsenT

YoungHA

ReedDS

2003 Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: evidence that dendritic cells are early and sustained targets of infection. Am J Pathol 163 2347 2370

24. LinderholmM

GroeneveldPH

TarnvikA

1996 Increased production of nitric oxide in patients with hemorrhagic fever with renal syndrome--relation to arterial hypotension and tumor necrosis factor. Infection 24 337 340

25. SanchezA

LukwiyaM

BauschD

MahantyS

SanchezAJ

2004 Analysis of human peripheral blood samples from fatal and nonfatal cases of Ebola (Sudan) hemorrhagic fever: cellular responses, virus load, and nitric oxide levels. J Virol 78 10370 10377

26. FeldmannH

BuganyH

MahnerF

KlenkHD

DrenckhahnD

1996 Filovirus-induced endothelial leakage triggered by infected monocytes/macrophages. J Virol 70 2208 2214

27. McCormickJB

KingIJ

WebbPA

JohnsonKM

O'SullivanR

1987 A case-control study of the clinical diagnosis and course of Lassa fever. J Infect Dis 155 445 455

28. PetersCJ

JahrlingPB

LiuCT

KenyonRH

McKeeKTJr

1987 Experimental studies of arenaviral hemorrhagic fevers. Curr Top Microbiol Immunol 134 5 68

29. WalkerDH

McCormickJB

JohnsonKM

WebbPA

Komba-KonoG

1982 Pathologic and virologic study of fatal Lassa fever in man. Am J Pathol 107 349 356

30. WinnWCJr

MonathTP

MurphyFA

WhitfieldSG

1975 Lassa virus hepatitis. Observations on a fatal case from the 1972 Sierra Leone epidemic. Arch Pathol 99 599 604

31. EdingtonGM

WhiteHA

1972 The pathology of Lassa fever. Trans R Soc Trop Med Hyg 66 381 389

32. FrameJD

BaldwinJMJr

GockeDJ

TroupJM

1970 Lassa fever, a new virus disease of man from West Africa. I. Clinical description and pathological findings. Am J Trop Med Hyg 19 670 676

33. McCormickJB

WalkerDH

KingIJ

WebbPA

ElliottLH

1986 Lassa virus hepatitis: a study of fatal Lassa fever in humans. Am J Trop Med Hyg 35 401 407

34. Fisher-HochSP

HutwagnerL

BrownB

McCormickJB

2000 Effective vaccine for lassa fever. J Virol 74 6777 6783

35. GeisbertTW

JonesS

FritzEA

ShurtleffAC

GeisbertJB

2005 Development of a new vaccine for the prevention of Lassa fever. PLoS Med 2 e183 doi:10.1371/journal.pmed.0020183

36. LukashevichIS

1985 Lassa virus lethality for inbred mice. Ann Soc Belg Med Trop 65 207 209

37. PascoloS

BervasN

UreJM

SmithAG

LemonnierFA

1997 HLA-A2.1-restricted education and cytolytic activity of CD8(+) T lymphocytes from beta2 microglobulin (beta2m) HLA-A2.1 monochain transgenic H-2Db beta2m double knockout mice. J Exp Med 185 2043 2051

38. JohnsonKM

McCormickJB

WebbPA

SmithES

ElliottLH

1987 Clinical virology of Lassa fever in hospitalized patients. J Infect Dis 155 456 464

39. FinkJ

GuF

VasudevanSG

2006 Role of T cells, cytokines and antibody in dengue fever and dengue haemorrhagic fever. Rev Med Virol 16 263 275

40. KileyMP

LangeJV

JohnsonKM

1979 Protection of rhesus monkeys from Lassa virus by immunisation with closely related Arenavirus. Lancet 2 738

41. LukashevichIS

PattersonJ

CarrionR

Moshkoffd

TicerA

2005 A live attenuated vaccine for Lassa fever made by reassortment of Lassa and Mopeia viruses. J Virol 79 13934 13942

42. BottenJ

AlexanderJ

PasquettoV

SidneyJ

BarrowmanP

2006 Identification of protective Lassa virus epitopes that are restricted by HLA-A2. J Virol 80 8351 8361

43. JahrlingPB

PetersCJ

1986 Serology and virulence diversity among Old-World arenaviruses, and the relevance to vaccine development. Med Microbiol Immunol (Berl) 175 165 167

44. CarrionRJr

BraskyK

MansfieldK

JohnsonC

GonzalesM

2007 Lassa virus infection in experimentally infected marmosets: liver pathology and immunophenotypic alterations in target tissues. J Virol 81 6482 6490

45. GordonS

2003 Alternative activation of macrophages. Nat Rev Immunol 3 23 35

46. StoutRD

SuttlesJ

XuJ

GrewalIS

FlavellRA

1996 Impaired T cell-mediated macrophage activation in CD40 ligand-deficient mice. J Immunol 156 8 11

47. TianL

NoelleRJ

LawrenceDA

1995 Activated T cells enhance nitric oxide production by murine splenic macrophages through gp39 and LFA-1. Eur J Immunol 25 306 309

48. ShuU

KiniwaM

WuCY

MaliszewskiC

VezzioN

1995 Activated T cells induce interleukin-12 production by monocytes via CD40-CD40 ligand interaction. Eur J Immunol 25 1125 1128

49. LowensteinCJ

PadalkoE

2004 iNOS (NOS2) at a glance. J Cell Sci 117 2865 2867

50. FongCH

BebienM

DidierlaurentA

NebauerR

HussellT

2008 An antiinflammatory role for IKKbeta through the inhibition of “classical” macrophage activation. J Exp Med 205 1269 1276

51. LangrishCL

McKenzieBS

WilsonNJ

de Waal MalefytR

KasteleinRA

2004 IL-12 and IL-23: master regulators of innate and adaptive immunity. Immunol Rev 202 96 105

52. BaizeS

KaplonJ

FaureC

PannetierD

Georges-CourbotMC

2004 Lassa virus infection of human dendritic cells and macrophages is productive but fails to activate cells. J Immunol 172 2861 2869

53. LukashevichIS

MaryankovaR

VladykoAS

NashkevichN

KoledaS

1999 Lassa and Mopeia virus replication in human monocytes/macrophages and in endothelial cells: different effects on IL-8 and TNF-alpha gene expression. J Med Virol 59 552 560

54. ZinkernagelRM

HaenselerE

LeistT

CernyA

HengartnerH

1986 T cell-mediated hepatitis in mice infected with lymphocytic choriomeningitis virus. Liver cell destruction by H-2 class I-restricted virus-specific cytotoxic T cells as a physiological correlate of the 51Cr-release assay? J Exp Med 164 1075 1092

55. SchumannJ

WolfD

PahlA

BruneK

PapadopoulosT

2000 Importance of Kupffer cells for T-cell-dependent liver injury in mice. Am J Pathol 157 1671 1683

56. SatoK

KadiiskaMB

GhioAJ

CorbettJ

FannYC

2002 In vivo lipid-derived free radical formation by NADPH oxidase in acute lung injury induced by lipopolysaccharide: a model for ARDS. FASEB J 16 1713 1720

57. ClarkIA

2007 The advent of the cytokine storm. Immunol Cell Biol 85 271 273

58. WherryEJ

BlattmanJN

Murali-KrishnaK

van der MostR

AhmedR

2003 Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J Virol 77 4911 4927

59. OehenS

HengartnerH

ZinkernagelRM

1991 Vaccination for disease. Science 251 195 198

60. JahrlingPB

SmithS

HesseRA

RhoderickJB

1982 Pathogenesis of Lassa virus infection in guinea pigs. Infect Immun 37 771 778

61. JahrlingPB

FrameJD

SmithSB

MonsonMH

1985 Endemic Lassa fever in Liberia. III. Characterization of Lassa virus isolates. Trans R Soc Trop Med Hyg 79 374 379

62. AlmeidaJR

PriceDA

PapagnoL

ArkoubZA

SauceD

2007 Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover. J Exp Med 204 2473 2485

63. KollerBH

MarrackP

KapplerJW

SmithiesO

1990 Normal development of mice deficient in beta 2M, MHC class I proteins, and CD8+ T cells. Science 248 1227 1230

64. KontgenF

SussG

StewartC

SteinmetzM

BluethmannH

1993 Targeted disruption of the MHC class II Aa gene in C57BL/6 mice. Int Immunol 5 957 964

65. LecompteE

Fichet-CalvetE

DaffisS

KoulemouK

SyllaO

2006 Mastomys natalensis and Lassa fever, West Africa. Emerg Infect Dis 12 1971 1974

66. AsperM

SternsdorfT

HassM

DrostenC

RhodeA

2004 Inhibition of different Lassa virus strains by alpha and gamma interferons and comparison with a less pathogenic arenavirus. J Virol 78 3162 3169

67. PinschewerDD

PerezM

JeetendraE

BächiT

HorvathE

2004 Kinetics of protective antibodies are determined by the viral surface antigen. J Clin Invest 114 988 993

68. MerklerD

HorvathE

BruckW

ZinkernagelRM

de la TorreJC

2006 “Viral déjà vu” elicits organ-specific immune disease independent of reactivity to self. J Clin Invest 116 1254 1263