[en] The alternative pathway of complement is an important innate defence against pathogens including ticks. This component of the immune system has selected for pathogens that have evolved countermeasures. Recently, a salivary protein able to inhibit the alternative pathway was cloned from the American tick Ixodes scapularis (Valenzuela et al., 2000; J. Biol. Chem. 275, 18717-18723). Here, we isolated two different sequences, similar to Isac, from the transcriptome of I. ricinus salivary glands. Expression of these sequences revealed that they both encode secreted proteins able to inhibit the complement alternative pathway. These proteins, called I. ricinus anticomplement (IRAC) protein I and II, are coexpressed constitutively in I. ricinus salivary glands and are upregulated during blood feeding. Also, we demonstrated that they are the products of different genes and not of alleles of the same locus. Finally, phylogenetic analyses demonstrate that ticks belonging to the Ixodes ricinus complex encode a family of relatively small anticomplement molecules undergoing diversification by positive Darwinian selection.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Daix, Virginie ; Université de Liège - ULiège > Immunologie et vaccinologie
Schroeder, Hélène ; Université de Liège - ULiège > Immunologie et vaccinologie
Praet, N.; Université de Liège - ULiège > Immunologie et vaccinologie
Georgin, J.-P.; Université de Liège - ULiège > Immunologie et vaccinologie
Chiappino, I.; Université de Liège - ULiège > Immunologie et vaccinologie
Gillet, Laurent ; Université de Liège - ULiège > Immunologie et vaccinologie
de Fays, K.; Université de Liège - ULiège > Immunologie et vaccinologie
Altekar, G., Dwarkadas, S., Huelsenbeck, J.P. and Ronquist, F. (2004) Parallel Metropolis coupled Markov chain Monte Carlo for Bayesian phylogenetic inference. Bioinformatics 20: 407-415.
Black, W.C.T. and Piesman, J. (1994) Phylogeny of hard- and soft-tick taxa (Acari: Ixodida) based on mitochondrial 16S rDNA sequences. Proc Natl Acad Sci USA 91: 10034-10038.
Blom, A.M. (2004) Strategies developed by bacteria and virus for protection from the human complement system. Scand J Clin Lab Invest 64: 479-496.
Coligan, J.E., Kruisbeek, A.M., Margulies, D.H., Shevach, E.M. and Strober, W. (1992) Current Protocols in Immunology. Greene Publishing Associates and Wiley-Interscience, New York.
Das, S., Banerjee, G., DePonte, K., Marcantonio, N., Kantor, F.S. and Fikrig, E. (2001) Salp25D, an Ixodes scapularis antioxidant, is 1 of 14 immunodominant antigens in engorged tick salivary glands. J Infect Dis 184: 1056-1064.
Duret, L. and Mouchiroud, D. (1999) Expression pattern and, surprisingly, gene length shape codon usage in Caenorhabditis, Drosophila, and Arabidopsis. Proc Natl Acad Sci USA 96: 4482-4487.
Francischetti, I.M., My Pham, V., Mans, B.J., Andersen, J.F., Mather, T.N., Lane, R.S. and Ribeiro, J.M. (2005) The transcriptome of the salivary glands of the female western blacklegged tick Ixodes pacificus (Acari: Ixodidae). Insect Biochem Mol Biol 35: 1142-1161.
Gillet, L., Daix, V., Donofrio, G., Wagner, M., Koszinowski, U.H., China, B., et al. (2005) Development of bovine herpesvirus 4 as an expression vector using bacterial artificial chromosome cloning. J Gen Virol 86: 907-917.
Hellwage, J., Meri, T., Heikkila, T., Alitalo, A., Panelius, J., Lahdenne, P., et al. (2001) The complement regulator factor H binds to the surface protein OspE of Borrelia burgdorferi. J Biol Chem 276: 8427-8435.
Houle, J.J. and Hoffmann, E.M. (1984) Evidence for restriction of the ability of complement to lyse homologous erythrocytes. J Immunol 133: 1444-1452.
Huelsenbeck, J.P. and Ronquist, F. (2001) MRBAYES: Bayesian inference of phylogenetic trees. Bioinformatics 17: 754-755.
Jones, D.T., Taylor, W.R. and Thornton, J.M. (1992) The rapid generation of mutation data matrices from protein sequences. Comput Appl Biosci 8: 275-282.
Keirans, J.E., Needham, G.R., Oliver, J.R. and J.H. (1999) The Ixodes (Ixodes) ricinus complex worldwide: diagnosis of the species in the complex, host and distribution. In Acarology IX: Symposia, pp. 341-347. Colombus, Ohio.
Kotwal, G.J. and Moss, B. (1988) Vaccinia virus encodes a secretory polypeptide structurally related to complement control proteins. Nature 335: 176-178.
Krushkal, J., Bat, O. and Gigli, I. (2000) Evolutionary relationships among proteins encoded by the regulator of complement activation gene cluster. Mol Biol Evol 17: 1718-1730.
Lawrie, C.H., Randolph, S.E. and Nuttall, P.A. (1999) Ixodes ticks: serum species sensitivity of anticomplement activity. Exp Parasitol 93: 207-214.
Lawrie, C.H., Sim, R.B. and Nuttall, P.A. (2005) Investigation of the mechanisms of anti-complement activity in Ixodes ricinus ticks. Mol Immunol 42: 31-38.
Li, W.H. (1993) Unbiased estimation of the rates of synonymous and nonsynonymous substitution. J Mol Evol 36: 96-99.
Limo, M.K., Voigt, W.P., Tumbo-Oeri, A.G., Njogu, R.M. and ole-MoiYoi, O.K. (1991) Purification and characterization of an anticoagulant from the salivary glands of the ixodid tick Rhipicephalus appendiculatus. Exp Parasitol 72: 418-429.
Mans, B.J. and Neitz, A.W. (2004) Adaptation of ticks to a bloodfeeding environment: evolution from a functional perspective. Insect Biochem Mol Biol 34: 1-17.
McLure, C.A., Dawkins, R.L., Williamson, J.F., Davies, R.A., Berry, J., Natalie, L.J., Laird, R. and Gaudieri, S. (2004) Amino acid patterns within short consensus repeats define conserved duplicons shared by genes of the RCA complex. J Mol Evol 59: 143-157.
Meri, S. and Jarva, H. (1998) Complement regulation. Vox Sang 74(Suppl. 2): 291-302.
Nunn, M.A., Sharma, A., Paesen, G.C., Adamson, S., Lissina, O., Willis, A.C. and Nuttall, P.A. (2005) Complement inhibitor of C5 activation from the soft tick Ornithodoros moubata. J Immunol 174: 2084-2091.
Rand, K.N., Moore, T., Sriskantha, A., Spring, K., Tellam, R., Willadsen, P. and Cobon, G.S. (1989) Cloning and expression of a protective antigen from the cattle tick Boophilus microplus. Proc Natl Acad Sci USA 86: 9657-9661.
Ribeiro, J.M., Makoul, G.T., Levine, J., Robinson, D.R. and Spielman, A. (1985) Antihemostatic, antiinflammatory, and immunosuppressive properties of the saliva of a tick, Ixodes dammini. J Exp Med 161: 332-344.
Ribeiro, J.M., Alarcon-Chaidez, F.I.M.B.F., Mans, B.J., Mather, T.N., Valenzuela, J.G. and Wikel, S.K. (2006) An annotated catalog of salivary gland transcripts from Ixodes scapularis ticks. Insect Biochem Mol Biol 36: 111-129.
Rodriguez de Cordoba, S., Lublin, D.M., Rubinstein, P. and Atkinson, J.P. (1985) Human genes for three complement components that regulate the activation of C3 are tightly linked. J Exp Med 161: 1189-1195.
Ronquist, F. and Huelsenbeck, J.P. (2003) MrBayes 3: Bayesian phylogenetic inference under mixed models. Bioinformatics 19: 1572-1574.
Rother, K., Till, G.O. and Hansch, G.M. (1998) The Complement System. Springer, Berlin.
Sharp, P.M. (1997) In search of molecular darwinism. Nature 385: 111-112.
Shields, D.C., Sharp, P.M., Higgins, D.G. and Wright, F. (1988) 'Silent' sites in Drosophila genes are not neutral: evidence of selection among synonymous codons. Mol Biol Evol 5: 704-716.
Soares, C.A., Lima, C.M., Dolan, M.C., Piesman, J., Beard, C.B. and Zeidner, N.S. (2005) Capillary feeding of specific dsRNA induces silencing of the isac gene in nymphal Ixodes scapularis ticks. Insect Mol Biol 14: 443-452.
Sonenshine, D.E. (1991) Biology of Ticks. Oxford University Press.
Sonenshine, D.E. (1993) Biology of Ticks. Oxford University Press.
Thern, A., Stenberg, L., Dahlback, B. and Lindahl, G. (1995) Igbinding surface proteins of Streptococcus pyogenes also bind human C4b-binding protein (C4BP), a regulatory component of the complement system. J Immunol 154: 375-386.
Thompson, J.D., Higgins, D.G. and Gibson, T.J. (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22: 4673-4680.
Valenzuela, J.G., Charlab, R., Mather, T.N. and Ribeiro, J.M. (2000) Purification, cloning, and expression of a novel salivary anticomplement protein from the tick, Ixodes scapularis. J Biol Chem 275: 18717-18723.
Vanderplasschen, A., Mathew, E., Hollinshead, M., Sim, R.B. and Smith, G.L. (1998) Extracellular enveloped vaccinia virus is resistant to complement because of incorporation of host complement control proteins into its envelope. Proc Natl Acad Sci USA 95: 7544-7549.
Vanderplasschen, A., Markine-Goriaynoff, N., Lomonte, P., Suzuki, M., Hiraoka, N., Yeh, J.C., et al. (2000) A multipotential beta-1,6-N-acetylglucosaminyl-transferase is encoded by bovine herpesvirus type 4. Proc Natl Acad Sci USA 97: 5756- 5761.
Wikel, S.K. (1979) Acquired resistance to ticks: expression of resistance by C4-deficient guinea pigs. Am J Trop Med Hyg 28: 586-590.
Willadsen, P., Riding, G.A., McKenna, R.V., Kemp, D.H., Tellam, R.L., Nielsen, J.N., et al. (1989) Immunologic control of a parasitic arthropod. Identification of a protective antigen from Boophilus microplus. J Immunol 143: 1346-1351.
Xu, G., Fang, Q.Q., Keirans, J.E. and Durden, L.A. (2003) Molecular phylogenetic analyses indicate that the Ixodes ricinus complex is a paraphyletic group. J Parasitol 89: 452-457.
Yamamoto, H., Blaas, P., Nicholson-Weller, A. and Hansch, G.M. (1990) Homologous species restriction of the complementmediated killing of nucleated cells. Immunology 70: 422-426.
Yang, Z. (1993) Maximum-likelihood estimation of phylogeny from DNA sequences when substitution rates differ over sites. Mol Biol Evol 10: 1396-1401.