Hostname: page-component-cd9895bd7-mkpzs Total loading time: 0 Render date: 2024-12-17T08:36:04.911Z Has data issue: false hasContentIssue false
  • English
  • Français

daf-7-related TGF-β homologues from Trichostrongyloid nematodes show contrasting life-cycle expression patterns

Published online by Cambridge University Press:  28 August 2009

H. J. McSORLEY ,
J. R. GRAINGER ,
Y. HARCUS ,
J. MURRAY ,
A. J. NISBET ,
D. P. KNOX  and
R. M. MAIZELS
H. J. McSORLEY
Affiliation:
Centre for Immunity, Infection and Evolution, and Institute for Immunology and Infection Research, Ashworth Laboratories, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, Scotland
J. R. GRAINGER
Affiliation:
Centre for Immunity, Infection and Evolution, and Institute for Immunology and Infection Research, Ashworth Laboratories, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, Scotland
Y. HARCUS
Affiliation:
Centre for Immunity, Infection and Evolution, and Institute for Immunology and Infection Research, Ashworth Laboratories, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, Scotland
J. MURRAY
Affiliation:
Centre for Immunity, Infection and Evolution, and Institute for Immunology and Infection Research, Ashworth Laboratories, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, Scotland
A. J. NISBET
Affiliation:
Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, Midlothian, EH26 0PZ, Scotland
D. P. KNOX
Affiliation:
Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, Midlothian, EH26 0PZ, Scotland
R. M. MAIZELS*
Affiliation:
Centre for Immunity, Infection and Evolution, and Institute for Immunology and Infection Research, Ashworth Laboratories, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, Scotland
*
*Corresponding author: Institute of Immunology and Infection Research, University of Edinburgh, Ashworth Laboratories, West Mains Road, Edinburgh EH9 3JT, Scotland. Fax: +44 131 650 5450. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

The transforming growth factor-β (TGF-β) gene family regulates critical processes in animal development, and plays a crucial role in regulating the mammalian immune response. We aimed to identify TGF-β homologues from 2 laboratory model nematodes (Heligmosomoides polygyrus and Nippostrongylus brasiliensis) and 2 major parasites of ruminant livestock (Haemonchus contortus and Teladorsagia circumcincta). Parasite cDNA was used as a template for gene-specific PCR and RACE. Homologues of the TGH-2 subfamily were isolated, and found to differ in length (301, 152, 349 and 305 amino acids respectively), with variably truncated N-terminal pre-proteins. All contained conserved C-terminal active domains (>85% identical over 115 amino acids) containing 9 cysteine residues, as in C. elegans DAF-7, Brugia malayi TGH-2 and mammalian TGF-β. Surprisingly, only the H. contortus homologue retained a conventional signal sequence, absent from shorter proteins of other species. RT-PCR assays of transcription showed that in H. contortus and N. brasiliensis expression was maximal in the infective larval stage, and very low in adult worms. In contrast, in H. polygyrus and T. circumcincta, tgh-2 transcription is higher in adults than infective larvae. The molecular evolution of this gene family in parasitic nematodes has diversified the pre-protein and life-cycle expression patterns of TGF-β homologues while conserving the structure of the active domain.

Keywords

developmentimmune modulatorstage-specific expression
Type
Research Article
Information
Parasitology , Volume 137 , Issue 1 , January 2010 , pp. 159 - 171
Copyright
Copyright © Cambridge University Press 2009

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

Affolter, M. and Basler, K. (2007). The decapentaplegic morphogen gradient: from pattern formation to growth regulation. Nature Reviews Genetics 8, 663–674.CrossRefGoogle ScholarPubMed
Anthony, R. M., Rutitzky, L. I., Urban, J. F. Jr., Stadecker, M. J. and Gause, W. C. (2007). Protective immune mechanisms in helminth infection. Nature Reviews Immunology 7, 975–987.CrossRefGoogle ScholarPubMed
Anthony, R. M., Urban, J. F. Jr., Alem, F., Hamed, H. A., Rozo, C. T., Boucher, J. L., Van Rooijen, N. and Gause, W. C. (2006). Memory TH2 cells induce alternatively activated macrophages to mediate protection against nematode parasites. Nature Medicine, 12, 955–960.CrossRefGoogle ScholarPubMed
Arasu, P. (2001). In vitro reactivation of Ancylostoma caninum tissue-arrested third-stage larvae by transforming growth factor-beta. Journal of Parasitology 87, 733–738.Google ScholarPubMed
Armour, J. and Duncan, M. (1987). Arrested larval development in cattle nematodes. Parasitology Today 3, 171–176.CrossRefGoogle ScholarPubMed
Beall, M. J. and Pearce, E. J. (2002). Transforming growth factor-β and insulin-like signaling pathways in parasitic helminths. International Journal for Parasitology 32, 399–404.CrossRefGoogle ScholarPubMed
Bird, D. M. and Riddle, D. L. (1994). A genetic nomenclature for parasitic nematodes. Journal of Nematology 26, 138–143.Google ScholarPubMed
Brand, A. M., Varghese, G., Majewski, W. and Hawdon, J. M. (2005). Identification of a DAF-7 ortholog from the hookworm Ancylostoma caninum. International Journal for Parasitology 35, 1489–1498.CrossRefGoogle ScholarPubMed
Brunner, A. M., Lioubin, M. N., Marquardt, H., Malacko, A. R., Wang, W. C., Shapiro, R. A., Neubauer, M., Cook, J., Madisen, L. and Purchio, A. F. (1992). Site-directed mutagenesis of glycosylation sites in the transforming growth factor-beta 1 (TGF β 1) and TGF β 2 (414) precursors and of cysteine residues within mature TGF β 1: effects on secretion and bioactivity. Molecular Endocrinology 6, 1691–1700.Google Scholar
Crook, M., Thompson, F. J., Grant, W. N. and Viney, M. E. (2005). daf-7 and the development of Strongyloides ratti and Parastongyloides trichosuri. Molecular and Biochemical Parasitology 139, 213–223.CrossRefGoogle ScholarPubMed
Elliott, D. E., Setiawan, T., Metwali, A., Blum, A., Urban, J. F. Jr. and Weinstock, J. V. (2004). Heligmosomoides polygyrus inhibits established colitis in IL-10-deficient mice. European Journal of Immunology 34, 2690–2698.CrossRefGoogle ScholarPubMed
Estevez, M., Attisano, L., Wrana, J. L., Albert, P. S., Massagué, J. and Riddle, D. L. (1993). The daf-4 gene encodes a bone morphogenetic protein receptor controlling C. elegans dauer larva development. Nature, London 365, 644–649.CrossRefGoogle ScholarPubMed
Finkelman, F. D., Shea-Donohue, T., Morris, S. C., Gildea, L., Strait, R., Madden, K. B., Schopf, L. and Urban, J. F. Jr. (2004). Interleukin-4- and interleukin-13-mediated host protection against intestinal nematode parasites. Immunological Reviews 201, 139–155.CrossRefGoogle ScholarPubMed
Finney, C. A., Taylor, M. D., Wilson, M. S. and Maizels, R. M. (2007). Expansion and activation of CD4+CD25+ regulatory T cells in Heligmosomoides polygyrus infection. European Journal of Immunology 37, 1874–1886.CrossRefGoogle ScholarPubMed
Freitas, T., Jung, E. and Pearce, E. J. (2007). TGF-β signaling controls embryo development in the parasitic flatworm Schistosoma mansoni. PLOS Pathogens 3, e52.CrossRefGoogle ScholarPubMed
Freitas, T. C. and Arasu, P. (2005). Cloning and characterisation of genes encoding two transforming growth factor-β-like ligands from the hookworm, Ancylostoma caninum. International Journal for Parasitology 35, 1477–1487.CrossRefGoogle ScholarPubMed
Geldhof, P., Murray, L., Couthier, A., Gilleard, J. S., McLauchlan, G., Knox, D. P. and Britton, C. (2006). Testing the efficacy of RNA interference in Haemonchus contortus. International Journal for Parasitology 36, 801–810.CrossRefGoogle ScholarPubMed
Gomez-Escobar, N., van den Biggelaar, A. and Maizels, R. M. (1997). A member of the TGF-β receptor gene family in the parasitic nematode Brugia. Gene 199, 101–109.CrossRefGoogle ScholarPubMed
Gomez-Escobar, N., Lewis, E. and Maizels, R. M. (1998). A novel member of the transforming growth factor-β (TGF-β) superfamily from the filarial nematodes Brugia malayi and B. pahangi. Experimental Parasitology 88, 200–209.CrossRefGoogle ScholarPubMed
Gomez-Escobar, N., Gregory, W. F. and Maizels, R. M. (2000). Identification of Bm-tgh-2, a filarial nematode homolog of C. elegans daf-7 and human TGF-β, expressed in microfilarial and adult stages of Brugia malayi. Infection and Immunity 68, 6402–6410.CrossRefGoogle ScholarPubMed
Gomez-Escobar, N., Bennett, C., Prieto-Lafuente, L., Aebischer, T., Blackburn, C. C. and Maizels, R. M. (2005). Heterologous expression of the filarial nematode alt gene products reveals their potential to inhibit immune function. BMC Biology 3, 1–16.CrossRefGoogle ScholarPubMed
Harcus, Y. M., Parkinson, J., Fernández, C., Daub, J., Selkirk, M. E., Blaxter, M. L. and Maizels, R. M. (2004). Signal sequence analysis of expressed sequence tags from the nematode Nippostrongylus brasiliensis and the evolution of secreted proteins in parasites. Genome Biology 5, R39.CrossRefGoogle ScholarPubMed
Hewitson, J. P., Harcus, Y. M., Curwen, R. S., Dowle, A. A., Atmadja, A. K., Ashton, P. D., Wilson, R. A. and Maizels, R. M. (2008). The secretome of the filarial parasite, Brugia malayi: proteomic profile of adult excretory-secretory products. Molecular and Biochemical Parasitology 160, 8–21.CrossRefGoogle ScholarPubMed
Hoberg, E. P. and Lichtenfels, J. R. (1994). Phylogenetic systematic analysis of the Trichostrongylidae (Nematoda), with an initial assessment of coevolution and biogeography. Journal of Parasitology 80, 976–996.CrossRefGoogle ScholarPubMed
Holland, M. J., Harcus, Y. M., Riches, P. L. and Maizels, R. M. (2000). Proteins secreted by the parasitic nematode Nippostrongylus brasiliensis act as adjuvants for Th2 responses. European Journal of Immunology 30, 1977–1987.3.0.CO;2-3>CrossRefGoogle ScholarPubMed
Hotez, P., Hawdon, J. and Schad, G. A. (1993). Hookworm larval infectivity, arrest and amphiparatenesis: the Caenorhabditis elegans Daf-c paradigm. Parasitology Today 9, 23–26.CrossRefGoogle ScholarPubMed
Hussein, A. S., Kichenin, K. and Selkirk, M. E. (2002). Suppression of secreted acetylcholinesterase expression in Nippostrongylus brasiliensis by RNA interference. Molecular and Biochemical Parasitology 122, 91–94.CrossRefGoogle ScholarPubMed
Inoue, T. and Thomas, J. H. (2000). Targets of TGF-β signaling in Caenorhabditis elegans dauer formation. Developmental Biology 217, 192–204.CrossRefGoogle ScholarPubMed
Knox, D. P. and Jones, D. G. (1990). Studies on the presence and release of proteolytic enzymes (proteinases) in gastro-intestinal nematodes of ruminants. International Journal for Parasitology 20, 243–249.CrossRefGoogle ScholarPubMed
Kotze, A. C. and Bagnall, N. H. (2006). RNA interference in Haemonchus contortus: suppression of β-tubulin gene expression in L3, L4 and adult worms in vitro. Molecular and Biochemical Parasitology 145, 101–110.CrossRefGoogle ScholarPubMed
Lawrence, R. A., Gray, C., Osborne, J. and Maizels, R. M. (1996). Nippostrongylus brasiliensis: Cytokine responses and nematode expulsion in normal and IL4-deficient mice. Experimental Parasitology 84, 65–73.CrossRefGoogle Scholar
Lendner, M., Doligalska, M., Lucius, R. and Hartmann, S. (2008). Attempts to establish RNA interference in the parasitic nematode Heligmosomoides polygyrus. Molecular and Biochemical Parasitology 161, 21–31.CrossRefGoogle ScholarPubMed
Li, M. O., Wan, Y. Y., Sanjabi, S., Robertson, A. K. and Flavell, R. A. (2006). Transforming growth factor-β regulation of immune responses. Annual Review of Immunology 24, 99–146.CrossRefGoogle ScholarPubMed
Luckhart, S., Crampton, A. L., Zamora, R., Lieber, M. J., Dos Santos, P. C., Peterson, T. M., Emmith, N., Lim, J., Wink, D. A. and Vodovotz, Y. (2003). Mammalian transforming growth factor b1 activated after ingestion by Anopheles stephensi modulates mosquito immunity. Infection and Immunity 71, 3000–3009.CrossRefGoogle Scholar
Maizels, R. M., Gomez-Escobar, N., Gregory, W. F., Murray, J. and Zang, X. (2001). Immune evasion genes from filarial nematodes. International Journal for Parasitology 31, 889–898.CrossRefGoogle ScholarPubMed
Maizels, R. M., Gomez-Escobar, N., Prieto-Lafuente, L., Murray, J. and Aebischer, T. (2008). Expression of helminth genes in Leishmania: an experimental transfection system to test immunological function. Parasite Immunology 30, 195–201.CrossRefGoogle ScholarPubMed
Massagué, J., Blain, S. W. and Lo, R. S. (2000). TGF-β signaling in growth control, cancer, and heritable disorders. Cell 103, 295–309.CrossRefGoogle ScholarPubMed
Massey, H. C., Castelletto, M. L., Bhopale, V. M., Schad, G. A. and Lok, J. B. (2005). Sst-tgh-1 from Strongyloides stercoralis encodes a proposed ortholog of daf-7 in Caenorhabditis elegans. Molecular and Biochemical Parasitology 142, 116–120.CrossRefGoogle ScholarPubMed
Morita, K., Flemming, A. J., Sugihara, Y., Mochii, M., Suzuki, Y., Yoshida, S., Wood, W. B., Kohara, Y., Leroi, A. M. and Ueno, N. (2002). A Caenorhabditis elegans TGF-β, DBL-1, controls the expression of LON-1, a PR-related protein, that regulates polyploidization and body length. EMBO Journal 21, 1063–1073.CrossRefGoogle ScholarPubMed
Newfeld, S. J., Wisotzkey, R. G. and Kumar, S. (1999). Molecular evolution of a developmental pathway: phylogenetic analyses of transforming growth factor-β family ligands, receptors and Smad signal transducers. Genetics 152, 783–795.CrossRefGoogle ScholarPubMed
Nisbet, A. J., Redmond, D. L., Matthews, J. B., Watkins, C., Yaga, R., Jones, J. T., Nath, M. and Knox, D. P. (2008). Stage-specific gene expression in Teladorsagia circumcincta (Nematoda: Strongylida) infective larvae and early parasitic stages. International Journal for Parasitology 38, 829–838.CrossRefGoogle ScholarPubMed
Ogawa, A., Streit, A., Antebi, A. and Sommer, R. J. (2009). A conserved endocrine mechanism controls the formation of dauer and infective larvae in nematodes. Current Biology 19, 67–71.CrossRefGoogle ScholarPubMed
Osman, A., Niles, E. G., Verjovski-Almeida, S. and LoVerde, P. T. (2006). Schistosoma mansoni TGF-β receptor II: role in host ligand-induced regulation of a schistosome target gene. PLOS Pathogens 2, e54.CrossRefGoogle ScholarPubMed
Parkinson, J., Mitreva, M., Whitton, C., Thomson, M., Daub, J., Martin, J., Schmid, R., Hall, N., Barrell, B., Waterston, R. H., McCarter, J. P. and Blaxter, M. L. (2004). A transcriptomic analysis of the phylum Nematoda. Nature Genetics 36, 1259–1267.CrossRefGoogle ScholarPubMed
Patterson, G. I. and Padgett, R. W. (2000). TGF β-related pathways. Roles in Caenorhabditis elegans development. Trends in Genetics 16, 27–33.CrossRefGoogle ScholarPubMed
Rausch, S., Huehn, J., Kirchhoff, D., Rzepecka, J., Schnoeller, C., Pillai, S., Loddenkemper, C., Scheffold, A., Hamann, A., Lucius, R. and Hartmann, S. (2008). Functional analysis of effector and regulatory T cells in a parasitic nematode infection. Infection and Immunity 76, 1908–1919.CrossRefGoogle Scholar
Redmond, D. L., Smith, S. K., Halliday, A., Smith, W. D., Jackson, F., Knox, D. P. and Matthews, J. B. (2006). An immunogenic cathepsin F secreted by the parasitic stages of Teladorsagia circumcincta. International Journal for Parasitology 36, 277–286.CrossRefGoogle ScholarPubMed
Ren, P., Lim, C.-S., Johnsen, R. J., Albert, P. S., Pilgrim, D. and Riddle, D. L. (1996). Control of C. elegans larval development by neuronal expression of a TGF-β homolog. Science 274, 1389–1391.CrossRefGoogle ScholarPubMed
Schallig, H. D. (2000). Immunological responses of sheep to Haemonchus contortus. Parasitology 120 (Suppl.), S63–S72.CrossRefGoogle ScholarPubMed
Suzuki, Y., Yandell, M. D., Roy, P. J., Krishna, S., Savage-Dunn, C., Ross, R. M., Padgett, R. W. and Wood, W. B. (1999). A BMP homolog acts as a dose-dependent regulator of body size and male tail patterning in Caenorhabditis elegans. Development 126, 241–250.CrossRefGoogle ScholarPubMed
Viney, M. E., Thompson, F. J. and Crook, M. (2005). TGF-β and the evolution of nematode parasitism. International Journal for Parasitology 35, 1473–1475.CrossRefGoogle ScholarPubMed
Voehringer, D., Shinkai, K. and Locksley, R. M. (2004). Type 2 immunity reflects orchestrated recruitment of cells committed to IL-4 production. Immunity 20, 267–277.CrossRefGoogle ScholarPubMed
Wilson, M. S., Taylor, M., Balic, A., Finney, C. A. M., Lamb, J. R. and Maizels, R. M. (2005). Suppression of allergic airway inflammation by helminth-induced regulatory T cells. Journal of Experimental Medicine 202, 1199–1212.CrossRefGoogle ScholarPubMed
Wolstenholme, A. J., Fairweather, I., Prichard, R., von Samson-Himmelstjerna, G. and Sangster, N. C. (2004). Drug resistance in veterinary helminths. Trends in Parasitology 20, 469–476.CrossRefGoogle ScholarPubMed
Zavala-Gongora, R., Kroner, A., Bernthaler, P., Knaus, P. and Brehm, K. (2006). A member of the transforming growth factor-β receptor family from Echinococcus multilocularis is activated by human bone morphogenetic protein 2. Molecular and Biochemical Parasitology 146, 265–271.CrossRefGoogle ScholarPubMed
Zawadzki, J. L., Presidente, P. J., Meeusen, E. N. and De Veer, M. J. (2006). RNAi in Haemonchus contortus: a potential method for target validation. Trends in Parasitology 22, 495–499.CrossRefGoogle ScholarPubMed