Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-23T12:10:25.802Z Has data issue: false hasContentIssue false
  • English
  • Français

Manipulation of host cytokine network by ticks: a potential gateway for pathogen transmission

Published online by Cambridge University Press:  12 November 2004

V. HAJNICKÁ ,
I. VANČOVÁ ,
P. KOCÁKOVÁ ,
M. SLOVÁK ,
J. GAšPERÍK ,
M. SLÁVIKOVÁ ,
R. S. HAILS ,
M. LABUDA  and
P. A. NUTTALL
V. HAJNICKÁ
Affiliation:
Institute of Virology, Slovak Academy of Sciences, 842 05 Bratislava, Slovakia
I. VANČOVÁ
Affiliation:
Institute of Virology, Slovak Academy of Sciences, 842 05 Bratislava, Slovakia
P. KOCÁKOVÁ
Affiliation:
Institute of Virology, Slovak Academy of Sciences, 842 05 Bratislava, Slovakia
M. SLOVÁK
Affiliation:
Institute of Zoology, Slovak Academy of Sciences, 842 05 Bratislava, Slovakia
J. GAšPERÍK
Affiliation:
Institute of Molecular Biology, Slovak Academy of Sciences, 842 05 Bratislava, Slovakia
M. SLÁVIKOVÁ
Affiliation:
Institute of Virology, Slovak Academy of Sciences, 842 05 Bratislava, Slovakia
R. S. HAILS
Affiliation:
NERC Centre for Ecology and Hydrology, Mansfield Road, Oxford OX1 3SR, UK
M. LABUDA
Affiliation:
Institute of Zoology, Slovak Academy of Sciences, 842 05 Bratislava, Slovakia
P. A. NUTTALL
Affiliation:
NERC Centre for Ecology and Hydrology, Mansfield Road, Oxford OX1 3SR, UK
Get access Rights & Permissions [Opens in a new window]

Abstract

Ticks are obligatory blood-feeding arthropods that secrete various immunomodulatory molecules to antagonize host inflammatory and immune responses. Cytokines play an important role in regulating these responses. We investigated the extent to which ticks interact with the sophisticated cytokine network by comparing the effect of salivary gland extracts (SGE) of 3 ixodid tick species, Dermacentor reticulatus, Amblyomma variegatum and Ixodes ricinus, all of which are important vectors of tick-borne pathogens. Using specific ELISAs, anti-cytokine activity was demonstrated with 7 cytokines: IL-8, MCP-1, MIP-1α, RANTES, eotaxin, IL-2 and IL-4. The results varied between species, and between adult males and females of the same species. Relatively high activity levels were detected in saliva of female D. reticulatus, confirming that the observed anti-cytokine activities are an integral part of tick saliva secreted into the host. Results with fractionated SGE indicated that from 2 to 6 putative cytokine binding molecules are produced, depending on species and sex. Binding ability of SGE molecules was verified by cross-linking with radio-isotope labelled MIP-1α. By targeting different cytokines, ixodid ticks can manipulate the cytokine network, which will greatly facilitate blood-feeding and provide a gateway for tick-borne pathogens that helps explain why ticks are such efficient and effective disease vectors.

Keywords

tick salivacytokine networkchemokineIL-8MCP-1MIP-1αRANTESeotaxinIL-2IL-4
Type
Research Article
Information
Parasitology , Volume 130 , Issue 3 , March 2005 , pp. 333 - 342
Copyright
2005 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

ALCAMI, A. ( 2003). Viral mimicry of cytokines, chemokines and their receptors. Nature Reviews of Immunology 3, 36–50.CrossRefGoogle Scholar
ALCAMI, A. & KOSZINOWSKI, U. H. ( 2000). Viral mechanisms of immune evasion. Immunology Today 21, 447–455.CrossRefGoogle Scholar
BRADFORD, M. M. ( 1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry 72, 248–254.CrossRefGoogle Scholar
CHARO, I. F., MYERS, S. J., HERMAN, A., FRANCI, C., CONNOLLY, A. J. & COUGHLIN, S. R. ( 1994). Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails. Proceedings of the National Academy of Sciences, USA 91, 2752–2756.CrossRefGoogle Scholar
CLARK-LEWIS, I., MOSER, B., WALZ, A., BAGGIOLINI, M., SCOTT, G. J. & AEBERSOLD, R. ( 1991). Chemical synthesis, purification, and characterization of two inflammatory proteins, neutrophil activating peptide 1 (interleukin-8) and neutrophil activating peptide. Biochemistry 30, 3128–3135.CrossRefGoogle Scholar
FERREIRA, B. R. & SILVA, J. S. ( 1999). Successive tick infestations selectively promote a T-helper 2 cytokine profile in mice. Immunology 96, 434–439.CrossRefGoogle Scholar
FUCHSBERGER, N., KITA, M., HAJNICKÁ, V., IMANISHI, J., LABUDA, M. & NUTTALL, P. A. ( 1995). Ixodid tick salivary gland extracts inhibit production of lipopolysaccharide-induced mRNA of several different human cytokines. Experimental and Applied Acarology 19, 671–676.CrossRefGoogle Scholar
GANAPAMO, F., RUTTI, B. & BROSSARD, M. ( 1995). In vitro production of interleukin-4 and interferon-gamma by lymph node cells from BALB/c mice infested with nymphal Ixodes ricinus ticks. Immunology 85, 120–124.Google Scholar
GANAPAMO, F., RUTTI, B. & BROSSARD, M. ( 1996). Cytokine production by lymph node cells from mice infested with Ixodes ricinus ticks and the effect of tick salivary gland extracts on IL-2 production. Scandinavian Journal of Immunology 44, 388–393.CrossRefGoogle Scholar
GALE, L. M. & McCOLL, S. R. ( 1999). Chemokines: extracellular messenger for all occasions? BioEssays 21, 17–28.Google Scholar
GILLESPIE, R. D., DOLAN, M. C., PIESMAN, J. & TITUS, R. G. ( 2001). Identification of an IL-2 binding protein in the saliva of the Lyme disease vector tick, Ixodes scapularis. Journal of Immunology 166, 4319–4327.CrossRefGoogle Scholar
HAJNICKÁ, V., FUCHSBERGER, N., SLOVÁK, M., KOCÁKOVÁ, P., LABUDA, M. & NUTTALL, P. A. ( 1998). Tick salivary gland extracts promote virus growth in vitro. Parasitology 116, 533–538.CrossRefGoogle Scholar
HAJNICKÁ, V., KOCÁKOVÁ, P., SLOVÁK, M., LABUDA, M., FUCHSBERGER, N. & NUTTALL, P. A. ( 2000). Inhibition of the antiviral action of interferon by tick salivary gland extract. Parasite Immunology 22, 201–206.CrossRefGoogle Scholar
HAJNICKÁ, V., KOCÁKOVÁ, P., SLÁVIKOVÁ, M., SLOVÁK, M., GAšPERÍK, J., FUCHSBERGER, N. & NUTTALL, P. A. ( 2001). Anti-interleukin-8 activity of tick salivary gland extracts. Parasite Immunology 23, 483–489.CrossRefGoogle Scholar
HANNIER, S., LIVERSIDGE, J., STERNBERG, J. M. & BOWMAN, A. S. ( 2003). Ixodes ricinus tick salivary gland extract inhibits IL-10 secretion and CD69 expression by mitogen-stimulated murine splenocytes and induces hyporesponsiveness in B lymphocytes. Parasite Immunology 25, 27–37.CrossRefGoogle Scholar
JONES, L. D., KAUFMAN, W. R. & NUTTALL, P. A. ( 1992). Modification of the skin feeding site by tick saliva mediates virus transmission. Experientia 48, 779–782.CrossRefGoogle Scholar
KOCÁKOVÁ, P., SLÁVIKOVÁ, M., HAJNICKÁ, V., SLOVÁK, M., GAšPERÍK, J., VANČOVÁ, I., FUCHSBERGER, N. & NUTTALL, P. A. ( 2003). Effect of fast protein liquid chromatography fractionated salivary gland extracts from different ixodid tick species on interleukin-8 binding to its cell receptors. Folia Parasitologia 50, 79–84.CrossRefGoogle Scholar
KOPECKY, J., KUTHEJLOVA, M., PECHOVA, J., LIN, J. X. & LEONARD, W. J. ( 1999). Salivary gland extract from Ixodes ricinus ticks inhibits production of interferon-gamma by the upregulation of interleukin-10. Parasite Immunology 21, 351–356.CrossRefGoogle Scholar
KROČOVÁ, Z., MACELA, A., HERNYCHOVÁ, L., KROČA, M., PECHOVÁ, J. & KOPECKÝ, J. ( 2003). Tick salivary gland extract accelerates proliferation of Francisella tularensis in the host. Journal of Parasitology 89, 14–20.CrossRefGoogle Scholar
KUBEš, M., FUCHSBERGER, N., LABUDA, M., ZUFFOVÁ, E. & NUTTALL, P. A. ( 1994). Salivary gland extracts of partially fed Dermacentor reticulatus ticks decrease natural killer cell activity in vitro. Immunology 82, 113–116.Google Scholar
LABUDA, M., JONES, L. D., WILLIAMS, T. & NUTTALL, P. A. ( 1993). Enhancement of tick-borne encephalitis virus transmission by tick salivary gland extracts. Medical and Veterinary Entomology 7, 193–196.CrossRefGoogle Scholar
LALANI, A. S., BARRETT, J. W. & McFADDEN, G. ( 2000). Modulating chemokines: more lessons from viruses. Immunology Today 21, 100–106.CrossRefGoogle Scholar
LEBOULLE, G., CRIPPA, M., DECREM, Y., MEJRI, N., BROSSARD, M., BOLLEN, A. & GODFROID, E. ( 2002). Characterization of a novel salivary immunosuppressive protein from Ixodes ricinus ticks. Journal of Biological Chemistry 277, 10083–10089.CrossRefGoogle Scholar
LUSSO, P. ( 2000). Chemokines and viruses: The dearest enemies. Virology 273, 228–240.CrossRefGoogle Scholar
MACALUSO, K. R. & WIKEL, S. K. ( 2001). Dermacentor andersoni: effects of repeated infestations on lymphocyte proliferation, cytokine production, and adhesion-molecule expression by BALB/c mice. Annals of Tropical Medicine and Parasitology 95, 413–427.CrossRefGoogle Scholar
MANTOVANI, A. ( 1999). The chemokine system: redundancy for robust outputs. Immunology Today 20, 254–257.CrossRefGoogle Scholar
MEJRI, N., RUTTI, B. & BROSSARD, M. ( 2002). Immunosuppressive effects of Ixodes ricinus tick saliva or salivary gland extracts on innate and acquired immune response of BALB/c mice. Parasitology Research 88, 192–197.CrossRefGoogle Scholar
MEJRI, N., FRANSCINI, N., RUTTI, B. & BROSSARD, M. ( 2001). Th2 polarization of the immune response of BALB/c mice to Ixodes ricinus instars, importance of several antigens in activation of specific Th2 subpopulations. Parasite Immunology 23, 61–69.CrossRefGoogle Scholar
NUTTALL, P. A. ( 1998). Displaced tick-parasite interactions at the host interface. Parasitology 116, S65–S72.CrossRefGoogle Scholar
NUTTALL, P. A., PAESEN, G. C., LAWRIE, C. & WANG, H. ( 2000). Vector-host interactions in disease transmission. Journal of Molecular Microbiology and Biotechnology 2, 381–386.Google Scholar
PECHOVÁ, J., šTEPÁNOVÁ, G., KOVÁŘ, L. & KOPECKÝ, J. ( 2002). Tick salivary gland extract-activated transmission of Borrelia afzelii spirochaetes. Folia Parasitologia 49, 153–159.CrossRefGoogle Scholar
PAESEN, G. C., ADAMS, P. L., HARLOS, K., NUTTALL, P. A. & STUART, D. I. ( 1999). Tick histamine-binding proteins: isolation, cloning, and three-dimensional structure. Molecular Cell 3, 661–671.CrossRefGoogle Scholar
PONATH, P. D., QIN, S., POST, T. W., WANG, J., WU, L., GERARD, N. P., NEWMAN, W., GERARD, C. & MACKAY, C. R. ( 1996). Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils. Journal of Experimental Medicine 183, 2437–2448.CrossRefGoogle Scholar
RAMACHANDRA, R. N. & WIKEL, S. K. ( 1992). Modulation of host-immune responses by ticks (Acari: Ixodidae): effect of salivary gland extracts on host macrophages and lymphocyte cytokine production. Journal of Medical Entomology 29, 818–826.CrossRefGoogle Scholar
ROBB, R. J., KUTNY, R. M., PANICO, M., MORRIS, H. R. & CHOWDHRY, V. ( 1984). Amino acid sequence and post-translational modification of human interleukin 2. Proceedings of the National Academy of Sciences, USA 81, 6486–6490.CrossRefGoogle Scholar
SCHOELER, G. B., MANWEILER, S. A. & WIKEL, S. K. ( 2000). Cytokine responses of C3H/HeN mice infested with Ixodes scapularis or Ixodes pacificus nymphs. Parasite Immunology 22, 31–40.CrossRefGoogle Scholar
SEET, B. T., SINGH, R., PAAVOLA, C., LAU, E. K., HANDEL, T. M. & McFADEN, G. ( 2001). Molecular determinants for CC-chemokine recognition by a poxvirus CC-chemokine inhibitor. Proceedings of the National Academy of Sciences, USA 98, 9008–9013.CrossRefGoogle Scholar
SLOVÁK, M., HAJNICKÁ, V., LABUDA, M. & FUCHSBERGER, N. ( 2000). Comparison of the protein profiles of salivary gland extracts derived from three species of unfed and partially fed ixodid ticks analysed by SDS-PAGE. Folia Parasitologia 47, 67–71.CrossRefGoogle Scholar
SONENSHINE, D. E. ( 1991). Biology of Ticks, 1st Edn. Oxford University Press, New York and Oxford.
SPELLBERG, B. & EDWARDS, J. E. Jr. ( 2001). Type 1/type 2 immunity in infectious disease. Clinical Infectious Disease 32, 76–102.CrossRefGoogle Scholar
WIKEL, S. K. ( 1999). Tick modulation of host immunity: an important factor in pathogen transmission. International Journal of Parasitology 29, 851–859.CrossRefGoogle Scholar
ZEIDNER, N., DREITZ, M., BELASCO, D. & FISH, D. ( 1996). Suppression of acute Ixodes scapularis-induced Borrelia burgdorferi infection using tumor necrosis factor-α, interleukin-2, and interferon-gamma. Journal of Infectious Diseases 173, 187–195.CrossRefGoogle Scholar
ZEIDNER, N., MBOW, M. L., DOLAN, M., MASSUNG, R., BACA, E. & PIESMAN, J. ( 1997). Effects of Ixodes scapularis and Borrelia burgdorferi on modulation of the host immune response: induction of a TH2 cytokine response in Lyme disease-susceptible (C3H/HeJ) mice but not in disease-resistant (BALB/c) mice. Infection and Immunity 65, 3100–3106.Google Scholar
ZEIDNER, N. S., SCHNEIDER, B. S., NUNCIO, M. S., GERN, L. & PIESMAN, J. ( 2002). Coinoculation of Borrelia spp. with tick salivary gland lysate enhances spirochaete load in mice and is tick species-specific. Journal of Parasitology 88, 1276–1278.Google Scholar