Background A human IgE response to Sm22.6 (a dominant IgE target in Schistosoma mansoni) is associated with the development of partial immunity. Located inside the tegument, the molecule belongs to a family of proteins from parasitic platyhelminths, the Tegument-Allergen-Like proteins (TALs). In addition to containing dynein-light-chain domains, these TALs also contain EF-hand domains similar to those found in numerous EF-hand allergens. Methodology/Principal Findings S. mansoni genome searches revealed 13 members (SmTAL1-13) within the species. Recent microarray data demonstrated they have a wide range of life-cycle transcriptional profiles. We expressed SmTAL1 (Sm22.6), SmTAL2, 3, 4, 5 and 13 as recombinant proteins and measured IgE and IgG4 in 200 infected males (7–60 years) from a schistosomiasis endemic region in Uganda. For SmTAL1 and 3 (transcribed in schistosomula through adult-worms and adult-worms, respectively) and SmTAL5 (transcribed in cercariae through adult-worms), detectable IgE responses were rare in 7–9 year olds, but increased with age. At all ages, IgE to SmTAL2 (expressed constitutively), was rare while anti-SmTAL2 IgG4 was common. Levels of IgE and IgG4 to SmTAL4 and 13 (transcribed predominantly in the cercariae/skin stage) were all low. Conclusions We have not measured SmTAL protein abundance or exposure in live parasites, but the antibody data suggests to us that, in endemic areas, there is priming and boosting of IgE to adult-worm SmTALs by occasional death of long-lived worms, desensitization to egg SmTALs through continuous exposure to dying eggs and low immunogenicity of larval SmTALs due to immunosuppression in the skin by the parasite. Of these, it is the gradual increase in IgE to the worm antigens that parallels age-dependent immunity seen in endemic areas.
References
[1]
Centers for Disease Control and Prevention website. Available: www.cdc.gov/parasites/schistosomiasis. Accessed 2012 Mar 1.
[2]
Kabatereine NB, Vennervald BJ, Ouma JH, Kemijumbi J, Butterworth AE, et al. (1999) Adult resistance to schistosomiasis mansoni: age-dependence of reinfection remains constant in communities with diverse exposure patterns. Parasitology 118: 101–5. doi: 10.1017/S0031182098003576
[3]
Fulford AJ, Butterworth AE, Ouma JH, Sturrock RF (1995) A statistical approach to schistosome population dynamics and estimation of the life-span of Schistosoma mansoni in man. Parasitology 110: 307–16. doi: 10.1017/S0031182000080896
[4]
Feldman GM, Dannenberg AM, Seed JL (1990) Physiologic oxygen tensions limit oxidant-mediated killing of schistosome eggs by inflammatory cells and isolated granulomas. J Leukoc Biol 47: 344–54.
[5]
Hagan P, Blumenthal UJ, Dunn D, Simpson AJ, Wilkins HA (1991) Human IgE, IgG4 and resistance to reinfection with Schistosoma haematobium. Nature 349: 243–245. doi: 10.1038/349243a0
[6]
Demeure CE, Rihet P, Abel L, Ouattara M, Bourgois A, et al. (1993) Resistance to Schistosoma mansoni in humans: influence of the IgE/IgG4 balance and IgG2 in immunity to reinfection after chemotherapy. J Infect Dis 168: 1000–1008. doi: 10.1093/infdis/168.4.1000
[7]
Rihet P, Demeure CE, Bourgois A, Prata A, Dessein AJ (1991) Evidence for an association between human resistance to Schistosoma mansoni and high anti-larval IgE levels. Eur J Immunol 21: 2679–2686. doi: 10.1002/eji.1830211106
[8]
Dunne DW, Butterworth AE, Fulford AJ, Kariuki HC, Langley JG, et al. (1992) Immunity after treatment of human schistosomiasis: association between IgE antibodies to adult worm antigens and resistance to reinfection. Eur J Immunol 6: 1483–1494. doi: 10.1002/eji.1830220622
[9]
Li Y, Sleigh AC, Ross AG, Li Y, Zhang X, et al. (2001) Human susceptibility to Schistosoma japonicum in China correlates with antibody isotypes to native antigens. Trans R Soc Trop Med Hyg 95: 441–448. doi: 10.1016/S0035-9203(01)90210-X
[10]
Aalberse RC, Stapel SO, Schuurman J, Rispens T (2009) Immunoglobulin G4: an odd antibody. Clin Exp Allergy 39: 469–477. doi: 10.1111/j.1365-2222.2009.03207.x
[11]
Capron M, Capron A (1994) Immunoglobulin E and effector cells in schistosomiasis. Science 264: 1876–7. doi: 10.1126/science.8009216
[12]
Dunne DW, Webster M, Smith P, Langley JG, Richardson BA, et al. (1997) The isolation of a 22 kDa band after SDS-PAGE of Schistosoma mansoni adult worms and its use to demonstrate that IgE responses against the antigen(s) it contains are associated with human resistance to reinfection. Parasite Immunol 19: 79–89. doi: 10.1046/j.1365-3024.1997.d01-186.x
[13]
Webster M, Fulford AJ, Braun G, Ouma JH, Kariuki HC, et al. (1996) Human immunoglobulin E responses to a recombinant 22.6-kilodalton antigen from Schistosoma mansoni adult worms are associated with low intensities of reinfection after treatment. Infect Immun 64: 4042–4046.
[14]
Pinot de Moira A, Fulford AJ, Kabatereine NB, Ouma JH, Booth M, et al. (2010) Analysis of complex patterns of human exposure and immunity to Schistosomiasis mansoni: the influence of age, sex, ethnicity and IgE. PLoS Negl Trop Dis 14: e820. doi: 10.1371/journal.pntd.0000820
[15]
Santiago ML, Hafalla JC, Kurtis JD, Aligui GL, Wiest PM, et al. (1998) Identification of the Schistosoma japonicum 22.6-kDa antigen as a major target of the human IgE response: similarity of IgE-binding epitopes to allergen peptides. Int Arch Allergy Immunol 117: 94–104. doi: 10.1159/000023995
[16]
Fitzsimmons CM, Stewart TJ, Hoffmann KF, Grogan JL, Yazdanbakhsh M, et al. (2004) Human IgE response to the Schistosoma haematobium 22.6 kDa antigen. Parasite Immunol 26: 371–376. doi: 10.1111/j.0141-9838.2004.00721.x
[17]
Vichasri-Grams S, Subpipattana P, Sobhon P, Viyanant V, Grams R (2006) An analysis of the calcium-binding protein 1 of Fasciola gigantica with a comparison to its homologs in the phylum Platyhelminthes. Mol Biochem Parasitol 146: 10–23. doi: 10.1016/j.molbiopara.2005.10.012
[18]
Francis P, Bickle Q (1992) Cloning of a 21.7-kDa vaccine-dominant antigen gene of Schistosoma mansoni reveals an EF hand-like motif. Mol Biochem Parasitol 50: 215–222. doi: 10.1016/0166-6851(92)90218-9
[19]
Hoffmann KF, Strand M (1997) Molecular characterization of a 20.8-kDa Schistosoma mansoni antigen: sequence similarity to tegumental associated antigens and dynein light chains. J Biol Chem 272: 14509–14515. doi: 10.1074/jbc.272.23.14509
[20]
Lopes DO, Paiva LF, Martins MA, Cardoso FC, Raj？o MA, et al. (2009) Sm21.6 a novel EF-hand family protein member located on the surface of Schistosoma mansoni adult worm that failed to induce protection against challenge infection but reduced liver pathology. Vaccine 27: 4127–4135. doi: 10.1016/j.vaccine.2009.04.068
[21]
Radauer C, Bublin M, Wagner S, Mari A, Breiteneder H (2008) Allergens are distributed into few protein families and possess a restricted number of biochemical functions. J Allergy Clin Immunol 121: 847–52. doi: 10.1016/j.jaci.2008.01.025
[22]
Fitzsimmons CM, Dunne DW (2009) Survival of the fittest: allergology or parasitology? Trends Parasitol 25: 447–451. doi: 10.1016/j.pt.2009.07.004
[23]
Black CL, Mwinzi PN, Muok EM, Abudho B, Fitzsimmons CM, et al. (2010) Influence of exposure history on the immunology and development of resistance to human Schistosomiasis mansoni. PLoS Negl Trop Dis 23: e637. doi: 10.1371/journal.pntd.0000637
[24]
Mohamed MM, Shalaby KA, LoVerde PT, Karim AM (1998) Characterization of Sm20.8, a member of a family of schistosome tegumental antigens. Mol Biochem Parasitol 96: 15–25. doi: 10.1016/S0166-6851(98)00088-7
[25]
Ruiz de Eguino AD, Machín A, Casais R, Castro AM, Boga JA, et al. (1999) Cloning and expression in Escherichia coli of a Fasciola hepatica gene encoding a calcium-binding protein. Mol Biochem Parasitol 101: 13–21. doi: 10.1016/S0166-6851(99)00012-2
[26]
Stein LD, David JR (1986) Cloning of a developmentally regulated tegument antigen of Schistosoma mansoni. Mol Biochem Parasitol 20: 253–264. doi: 10.1016/0166-6851(86)90106-4
[27]
Li Y, Auliff A, Jones MK, Yi X, McManus DP (2000) Immunogenicity and immunolocalization of the 22.6 kDa antigen of Schistosoma japonicum. Parasite Immunol 22: 415–24. doi: 10.1046/j.1365-3024.2000.00319.x
[28]
Chen J, Xu H, Zhang Z, Zeng S, Gan W, et al. (2011) Cloning and expression of 21.1-kDa tegumental protein of Clonorchis sinensis and human antibody response to it as a trematode-nematode pan-specific serodiagnosis antigen. Parasitol Res 108: 161–168. doi: 10.1007/s00436-010-2050-4
[29]
Fitzsimmons CM, McBeath R, Joseph S, Jones FM, Walter K, et al. (2007) Factors affecting human IgE and IgG responses to allergen-like Schistosoma mansoni antigens: Molecular structure and patterns of in vivo exposure. Int Arch Allergy Immunol 142: 40–50. doi: 10.1159/000095997
[30]
Berriman M, Haas BJ, LoVerde PT, Wilson RA, Dillon GP, et al. (2009) The genome of the blood fluke Schistosoma mansoni. Nature 460: 352–8. doi: 10.1038/nature08160
[31]
Fitzpatrick JM, Peak E, Perally S, Chalmers IW, Barrett J, et al. (2009) Anti-schistosomal intervention targets identified by lifecycle transcriptomic analyses. PLoS Negl Trop Dis 3: e543. doi: 10.1371/journal.pntd.0000543
[32]
Chalmers IW, McArdle AJ, Coulson RM, Wagner MA, Schmid R, et al. (2008) Developmentally regulated expression, alternative splicing and distinct sub-groupings in members of the Schistosoma mansoni venom allergen-like (SmVAL) gene family. BMC Genomics 23: 89. doi: 10.1186/1471-2164-9-89
[33]
ArrayExpress. Available: http://www.ebi.ac.uk/miamexpress/. Accessed 2012 Mar 1.
[34]
GeneDB website. Available: http://www.genedb.org/Homepage/Smansoni. Accessed 2012 Mar 1.
[35]
Naus CWA, Booth M, Jones FM, Kemijumbi J, Vennervald BJ, et al. (2003) The relationship between age, sex, egg-count and specific antibody responses against Schistosoma mansoni antigens in a Ugandan fishing community. Int J Trop Med Hyg 8: 561–568.
[36]
Steinitz M, Baraz L (2000) A rapid method for estimating the binding of ligands to ELISA microwells. J Immunol Methods 238(1–2): 143–50. doi: 10.1016/S0022-1759(00)00160-5
[37]
Nanduri J, Dennis JE, Rosenberry TL, Mahmoud AA, Tartakoff AM (1991) Glycocalyx of bodies versus tails of Schistosoma mansoni cercariae. Lectin-binding, size, charge, and electron microscopic characterization. J Biol Chem 266: 1341–7.
[38]
Fitzsimmons CM, Schramm G, Jones FM, Chalmers IW, Hoffmann KF, et al. (2005) Molecular characterization of omega-1: a hepatotoxic ribonuclease from Schistosoma mansoni eggs. Mol Biochem Parasitol 144: 123–127. doi: 10.1016/j.molbiopara.2005.08.003
[39]
Skelly PJ, Shoemaker CB (2001) The Schistosoma mansoni host-interactive tegument forms from vesicle eruptions of a cyton network. Parasitology 122: 67–73. doi: 10.1017/S0031182000007071
[40]
Braschi S, Curwen RS, Ashton PD, Verjovski-Almeida S, Wilson A (2006) The tegument surface membranes of the human blood parasite Schistosoma mansoni: a proteomic analysis after differential extraction. Proteomics 6: 1471–82. doi: 10.1002/pmic.200500368
[41]
Wilson RA, Barnes PE (1974) The tegument of Schistosoma mansoni: observations on the formation, structure and composition of cytoplasmic inclusions in relation to tegument function. Parasitology 68: 239–58.
[42]
Hockley DJ, McLaren DJ (1973) Schistosoma mansoni: changes in the outer membrane of the tegument during development from cercaria to adult worm. Int J Parasitol 3: 13–25. doi: 10.1016/0020-7519(73)90004-0
[43]
Hansell E, Braschi S, Medzihradszk KF, Sajid M, Debnath M, et al. (2008) Proteomic analysis of skin invasion by blood fluke larvae. PLoS Negl Trop Dis 2: e262. doi: 10.1371/journal.pntd.0000262
[44]
Hall SL, Braschi S, Truscott M, Mathieson W, Cesari IM, et al. (2011) Insights into blood feeding by schistosomes from a proteomic analysis of worm vomitus. Mol Biochem Parasitol 179: 18–29. doi: 10.1016/j.molbiopara.2011.05.002
[45]
Fallon PG, Fookes RE, Wharton GA (1996) Temporal differences in praziquantel- and oxamniquine-induced tegumental damage to adult Schistosoma mansoni: implications for drug-antibody synergy. Parasitology 112: 47–58. doi: 10.1017/S0031182000065069
[46]
Skelly PJ, Shoemaker CB (2001) The Schistosoma mansoni host-interactive tegument forms from vesicle eruptions of a cyton network. Parasitology 122: 67–73. doi: 10.1017/S0031182000007071
[47]
Woolhouse ME, Hagan P (1999) Seeking the ghost of worms past. Nat Med 5: 1225–7. doi: 10.1038/15169
[48]
Wilson RA, Coulson PS, Sturrock RF, Reid GD (1990) Schistosome migration in primates: a study in the olive baboon (Papio anubis). Trans R Soc Trop Med Hyg 84: 80–3. doi: 10.1016/0035-9203(90)90391-Q
[49]
Jenkins SJ, Hewitson JP, Jenkins GR, Mountford AP (2005) Modulation of the host's immune response by schistosome larvae. Parasite Immunol 27: 385–93. doi: 10.1111/j.1365-3024.2005.00789.x
[50]
He YX, Chen L, Ramaswamy K (2002) Schistosoma mansoni, S. haematobium, and S. japonicum: early events associated with penetration and migration of schistosomula through human skin. Exp Parasitol 102: 99–108. doi: 10.1016/S0014-4894(03)00024-9
[51]
Angeli V, Faveeuw C, Roye O, Fontaine J, Teissier E, et al. (2001) Role of the parasite-derived prostaglandin D2 in the inhibition of epidermal Langerhans cell migration during schistosomiasis infection. J Exp Med 193: 1135–47. doi: 10.1084/jem.193.10.1135
[52]
Whitfield PJ, Bartlett A, Khammo N, Brain AP, Brown MB, et al. (2003) Delayed tail loss during the invasion of human skin by schistosome cercariae. Parasitology 126: 135–40. doi: 10.1017/S0031182002002676
