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 LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2010 Číslo 11
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
Najčítanejšie v tomto čísle
- Zn Inhibits Coronavirus and Arterivirus RNA Polymerase Activity and Zinc Ionophores Block the Replication of These Viruses in Cell Culture
- The Female Lower Genital Tract Is a Privileged Compartment with IL-10 Producing Dendritic Cells and Poor Th1 Immunity following Infection
- Crystal Structure and Size-Dependent Neutralization Properties of HK20, a Human Monoclonal Antibody Binding to the Highly Conserved Heptad Repeat 1 of gp41
- The Arabidopsis Resistance-Like Gene Is Activated by Mutations in and Contributes to Resistance to the Bacterial Effector AvrRps4