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Tick Histamine Release Factor Is Critical for Engorgement and Transmission of the Lyme Disease Agent


Ticks are distributed worldwide and affect human and animal health by transmitting diverse infectious agents. Effective vaccines against most tick-borne pathogens are not currently available. In this study, we characterized a tick histamine release factor (tHRF) from Ixodes scapularis and addressed the vaccine potential of this antigen in the context of tick engorgement and B. burgdorferi transmission. Results from western blotting and quantitative Reverse Transcription-PCR showed that tHRF is secreted in tick saliva, and upregulated in Borrelia burgdorferi-infected ticks. Further, the expression of tHRF was coincident with the rapid feeding phase of the tick, suggesting a role for tHRF in tick engorgement and concomitantly, for efficient B. burgdorferi transmission. Silencing tHRF by RNA interference (RNAi) significantly impaired tick feeding and decreased B. burgdorferi burden in mice. Interfering with tHRF by actively immunizing mice with recombinant tHRF, or passively transferring tHRF antiserum, also markedly reduced the efficiency of tick feeding and B. burgdorferi burden in mice. Recombinant tHRF was able to bind to host basophils and stimulate histamine release. Therefore, we speculate that tHRF might function in vivo to modulate vascular permeability and increase blood flow to the tick bite-site, facilitating tick engorgement. These findings suggest that blocking tHRF might offer a viable strategy to complement ongoing efforts to develop vaccines to block tick feeding and transmission of tick-borne pathogens.


Vyšlo v časopise: Tick Histamine Release Factor Is Critical for Engorgement and Transmission of the Lyme Disease Agent. PLoS Pathog 6(11): e32767. doi:10.1371/journal.ppat.1001205
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001205

Souhrn

Ticks are distributed worldwide and affect human and animal health by transmitting diverse infectious agents. Effective vaccines against most tick-borne pathogens are not currently available. In this study, we characterized a tick histamine release factor (tHRF) from Ixodes scapularis and addressed the vaccine potential of this antigen in the context of tick engorgement and B. burgdorferi transmission. Results from western blotting and quantitative Reverse Transcription-PCR showed that tHRF is secreted in tick saliva, and upregulated in Borrelia burgdorferi-infected ticks. Further, the expression of tHRF was coincident with the rapid feeding phase of the tick, suggesting a role for tHRF in tick engorgement and concomitantly, for efficient B. burgdorferi transmission. Silencing tHRF by RNA interference (RNAi) significantly impaired tick feeding and decreased B. burgdorferi burden in mice. Interfering with tHRF by actively immunizing mice with recombinant tHRF, or passively transferring tHRF antiserum, also markedly reduced the efficiency of tick feeding and B. burgdorferi burden in mice. Recombinant tHRF was able to bind to host basophils and stimulate histamine release. Therefore, we speculate that tHRF might function in vivo to modulate vascular permeability and increase blood flow to the tick bite-site, facilitating tick engorgement. These findings suggest that blocking tHRF might offer a viable strategy to complement ongoing efforts to develop vaccines to block tick feeding and transmission of tick-borne pathogens.


Zdroje

1. de la FuenteJ

KocanKM

AlmazanC

BlouinEF

2008 Targeting the tick-pathogen interface for novel control strategies. Front Biosci 13 6947 6956

2. AndersonJF

MagnarelliLA

2008 Biology of ticks. Infect Dis Clin North Am 22 195 215, v

3. FederHMJr

JohnsonBJ

O'ConnellS

ShapiroED

SteereAC

2007 A critical appraisal of “chronic Lyme disease”. N Engl J Med 357 1422 1430

4. ClarkRP

HuLT

2008 Prevention of lyme disease and other tick-borne infections. Infect Dis Clin North Am 22 381 396, vii

5. NardelliDT

MunsonEL

CallisterSM

SchellRF

2009 Human Lyme disease vaccines: past and future concerns. Future Microbiol 4 457 469

6. SteereAC

SikandVK

MeuriceF

ParentiDL

FikrigE

1998 Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. Lyme Disease Vaccine Study Group. N Engl J Med 339 209 215

7. de la FuenteJ

KocanKM

BlouinEF

2007 Tick vaccines and the transmission of tick-borne pathogens. Vet Res Commun 31 Suppl 1 85 90

8. AllenJR

HumphreysSJ

1979 Immunisation of guinea pigs and cattle against ticks. Nature 280 491 493

9. KotsyfakisM

AndersonJM

AndersenJF

CalvoE

FrancischettiIM

2008 Cutting edge: Immunity against a “silent” salivary antigen of the Lyme vector Ixodes scapularis impairs its ability to feed. J Immunol 181 5209 5212

10. LabudaM

TrimnellAR

LickovaM

KazimirovaM

DaviesGM

2006 An antivector vaccine protects against a lethal vector-borne pathogen. PLoS Pathog 2 e27

11. BrownSJ

AskenasePW

1981 Cutaneous basophil responses and immune resistance of guinea pigs to ticks: passive transfer with peritoneal exudate cells or serum. J Immunol 127 2163 2167

12. WikelSK

1996 Host immunity to ticks. Annu Rev Entomol 41 1 22

13. NarasimhanS

DeponteK

MarcantonioN

LiangX

RoyceTE

2007 Immunity against Ixodes scapularis salivary proteins expressed within 24 hours of attachment thwarts tick feeding and impairs Borrelia transmission. PLoS ONE 2 e451

14. De SilvaAM

FikrigE

1995 Growth and migration of Borrelia burgdorferi in Ixodes ticks during blood feeding. Am J Trop Med Hyg 53 397 404

15. BrossardM

WikelSK

2004 Tick immunobiology. Parasitology 129 Suppl S161 176

16. PiesmanJ

OliverJR

SinskyRJ

1990 Growth kinetics of the Lyme disease spirochete (Borrelia burgdorferi) in vector ticks (Ixodes dammini). Am J Trop Med Hyg 42 352 357

17. FrancischettiIM

Sa-NunesA

MansBJ

SantosIM

RibeiroJM

2009 The role of saliva in tick feeding. Front Biosci 14 2051 2088

18. HoviusJW

LeviM

FikrigE

2008 Salivating for knowledge: potential pharmacological agents in tick saliva. PLoS Med 5 e43

19. RibeiroJM

Alarcon-ChaidezF

FrancischettiIM

MansBJ

MatherTN

2006 An annotated catalog of salivary gland transcripts from Ixodes scapularis ticks. Insect Biochem Mol Biol 36 111 129

20. KempDH

BourneA

1980 Boophilus microplus: the effect of histamine on the attachment of cattle-tick larvae–studies in vivo and in vitro. Parasitology 80 487 496

21. PaesenGC

AdamsPL

HarlosK

NuttallPA

StuartDI

1999 Tick histamine-binding proteins: isolation, cloning, and three-dimensional structure. Mol Cell 3 661 671

22. MulengaA

MacalusoKR

SimserJA

AzadAF

2003 The American dog tick, Dermacentor variabilis, encodes a functional histamine release factor homolog. Insect Biochem Mol Biol 33 911 919

23. NarasimhanS

SukumaranB

BozdoganU

ThomasV

LiangX

2007 A tick antioxidant facilitates the Lyme disease agent's successful migration from the mammalian host to the arthropod vector. Cell Host Microbe 2 7 18

24. VonakisBM

MacglashanDWJr

VilarinoN

LangdonJM

ScottRS

2008 Distinct characteristics of signal transduction events by histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP)-induced priming and activation of human basophils. Blood 111 1789 1796

25. NuttallPA

PaesenGC

LawrieCH

WangH

2000 Vector-host interactions in disease transmission. J Mol Microbiol Biotechnol 2 381 386

26. DaiJ

WangP

AdusumilliS

BoothCJ

NarasimhanS

2009 Antibodies against a tick protein, Salp15, protect mice from the Lyme disease agent. Cell Host Microbe 6 482 492

27. RamamoorthiN

NarasimhanS

PalU

BaoF

YangXF

2005 The Lyme disease agent exploits a tick protein to infect the mammalian host. Nature 436 573 577

28. BommerUA

ThieleBJ

2004 The translationally controlled tumour protein (TCTP). Int J Biochem Cell Biol 36 379 385

29. MacDonaldSM

RafnarT

LangdonJ

LichtensteinLM

1995 Molecular identification of an IgE-dependent histamine-releasing factor. Science 269 688 690

30. MacDonaldSM

BhisutthibhanJ

ShapiroTA

RogersonSJ

TaylorTE

2001 Immune mimicry in malaria: Plasmodium falciparum secretes a functional histamine-releasing factor homolog in vitro and in vivo. Proc Natl Acad Sci U S A 98 10829 10832

31. MulengaA

MacalusoKR

SimserJA

AzadAF

2003 Dynamics of Rickettsia-tick interactions: identification and characterization of differentially expressed mRNAs in uninfected and infected Dermacentor variabilis. Insect Mol Biol 12 185 193

32. MulengaA

AzadAF

2005 The molecular and biological analysis of ixodid ticks histamine release factors. Exp Appl Acarol 37 215 229

33. BartleyK

NisbetAJ

OfferJE

SparksNH

WrightHW

2009 Histamine release factor from Dermanyssus gallinae (De Geer): characterization and in vitro assessment as a protective antigen. Int J Parasitol 39 447 456

34. PaineSH

KempDH

AllenJR

1983 In vitro feeding of Dermacentor andersoni (Stiles): effects of histamine and other mediators. Parasitology 86 (Pt 3) 419 428

35. MansBJ

2005 Tick histamine-binding proteins and related lipocalins: potential as therapeutic agents. Curr Opin Investig Drugs 6 1131 1135

36. Dunham-EmsSM

CaimanoMJ

PalU

WolgemuthCW

EggersCH

2009 Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks. J Clin Invest 119 3652 3665

37. NarasimhanS

MontgomeryRR

DePonteK

TschudiC

MarcantonioN

2004 Disruption of Ixodes scapularis anticoagulation by using RNA interference. Proc Natl Acad Sci U S A 101 1141 1146

38. AnguitaJ

RamamoorthiN

HoviusJW

DasS

ThomasV

2002 Salp15, an ixodes scapularis salivary protein, inhibits CD4(+) T cell activation. Immunity 16 849 859

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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