1921
Volume 81, Issue 3
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Human African trypanosomiasis is a neglected disease caused by spp. A parasite cation pump (Ca ATPase; TBCA2) essential for survival and cation homeostasis was identified and characterized. It was hypothesized that targeting this pump using a ghost (VCG)-based vaccine could protect against murine infection. mRNA and protein expression of TBCA2 was differentially expressed in blood and insect stages of parasites and immunolocalized in the pericellular membrane and the flagellar pocket of bloodstream forms. Antigen-specific antibodies and Th1 cytokines, interleukin-2, interferon-gamma, and tumor necrosis factor-alpha were induced in rVCG-TBCA2-immunized mice and on antigen stimulation of splenic immune T cells, but the corresponding Th2-type response was unremarkable. Despite an increased median survival of 6 days in vaccinated mice, the mice were not protected against infection. Thus, immunization of mice produced robust parasite-specific antibodies but failed to protect mice against parasite challenge.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.2009.81.407
2009-09-01
2017-09-24
Loading full text...

Full text loading...

/deliver/fulltext/14761645/81/3/0810407.html?itemId=/content/journals/10.4269/ajtmh.2009.81.407&mimeType=html&fmt=ahah

References

  1. Fevre EM, Picozzi K, Jannin J, Welburn SC, Maudlin I, 2006. Human African trypanosomiasis. Epidemiol Control 61 : 167–221.
  2. Bouteille B, Oukem O, Bisser S, Dumas M, 2003. Treatment perspectives for human African trypanosomiasis. Fundam Clin Pharmacol 17 : 171–181.
  3. Fraser-L’Hostis C, frise-Quertain F, Coral D, Deshusses J, 1997. Regulation of the intracellular pH in the protozoan parasite Trypanosoma brucei brucei. Biol Chem 378 : 1039–1046.
  4. Benaim G, Lopez-Estrano C, Docampo R, Moreno SN, 1993. A calmodulin-stimulated Ca2+ pump in plasma-membrane vesicles from Trypanosoma brucei; selective inhibition by pentamidine. Biochem J 296 : 759–763.
  5. Docampo R, Gadelha FR, Moreno SN, Benaim G, Hoffmann ME, Vercesi AE, 1993. Disruption of Ca2+ homeostasis in Trypanosoma cruzi by crystal violet. J Eukaryot Microbiol 40 : 311–316.
  6. Vercesi AE, Moreno SN, Bernardes CF, Meinicke AR, Fernandes EC, Docampo R, 1993. Thapsigargin causes Ca2+ release and collapse of the membrane potential of Trypanosoma brucei mitochondria in situ and of isolated rat liver mitochondria. J Biol Chem 268 : 8564–8568.
  7. Catisti R, Uyemura SA, Docampo R, Vercesi AE, 2000. Calcium mobilization by arachidonic acid in trypanosomatids. Mol Biochem Parasitol 105 : 261–271.
  8. Parsons M, Ruben L, 2000. Pathways involved in environmental sensing in trypanosomatids. Parasitol Today 16 : 56–62.
  9. Lu HG, Zhong L, de Souza W, Benchimol M, Moreno S, Docampo R, 1998. Ca2+ content and expression of an acidocalcisomal calcium pump are elevated in intracellular forms of Trypanosoma cruzi. Mol Cell Biol 18 : 2309–2323.
  10. Luo S, Ruiz FA, Moreno SN, 2005. The acidocalcisome Ca2+-ATPase (TgA1) of Toxoplasma gondii is required for polyphosphate storage, intracellular calcium homeostasis and virulence. Mol Microbiol 55 : 1034–1045.
  11. Moreno SN, Docampo R, Vercesi AE, 1992. Calcium homeostasis in procyclic and bloodstream forms of Trypanosoma brucei. Lack of inositol 1,4,5-trisphosphate-sensitive Ca2+ release. J Biol Chem 267 : 6020–6026.
  12. Nolan DP, Reverlard P, Pays E, 1994. Overexpression and characterization of a gene for a Ca(2+)-ATPase of the endoplasmic reticulum in Trypanosoma brucei. J Biol Chem 269 : 26045–26051.
  13. Luo S, Rohloff P, Cox J, Uyemura SA, Docampo R, 2004. Trypanosoma brucei plasma membrane-type Ca(2+)-ATPase 1 (TbPMC1) and 2 (TbPMC2) genes encode functional Ca(2+)-ATPases localized to the acidocalcisomes and plasma membrane, and essential for Ca(2+) homeostasis and growth. J Biol Chem 279 : 14427–14439.
  14. Walter RD, Opperdoes FR, 1982. Subcellular distribution of ade-nylate cyclase, cyclic-AMP phosphodiesterase, protein kinases and phosphoprotein phosphatase in Trypanosoma brucei. Mol Biochem Parasitol 6 : 287–295.
  15. Coppens I, Opperdoes FR, Courtoy PJ, Baudhuin P, 1987. Receptor-mediated endocytosis in the bloodstream form of Trypanosoma brucei. J Protozool 34 : 465–473.
  16. Coppens I, Baudhuin P, Opperdoes FR, Courtoy PJ, 1988. Receptors for the host low density lipoproteins on the hemofla-gellate Trypanosoma brucei: purification and involvement in the growth of the parasite. Proc Natl Acad Sci USA 85 : 6753–6757.
  17. Stijlemans B, Conrath K, Cortez-Retamozo V, Van Xong H, Wyns L, Senter P, Revets H, De Baetselier P, Muyldermans S, Magez S, 2004. Efficient targeting of conserved cryptic epitopes of infectious agents by single domain antibodies. African trypanosomes as paradigm. J Biol Chem 279 : 1256–1261.
  18. Olenick JG, Wolff R, Nauman RK, McLaughlin J, 1988. A flagellar pocket membrane fraction from Trypanosoma brucei rhodesiense: immunogold localization and nonvariant immunoprotection. Infect Immun 56 : 92–98.
  19. McLaughlin J, 1987. Trypanosoma rhodesiense: antigenicity and immunogenicity of flagellar pocket membrane components. Exp Parasitol 64 : 1–11.
  20. Hamadien M, Lycke N, Bakhiet M, 1999. Induction of the trypanosome lymphocyte-triggering factor (TLTF) and neutralizing antibodies to the TLTF in experimental african trypanosomiasis. Immunology 96 : 606–611.
  21. Stiles JK, Kucerova Z, Sarfo B, Meade CA, Thompson W, Shah P, Xue L, Meade JC, 2003. Identification of surface-membrane P-type ATPases resembling fungal K(+)- and Na(+)-ATPases, in Trypanosoma brucei, Trypanosoma cruzi and Leishmania donovani. Ann Trop Med Parasitol 97 : 351–366.
  22. Marchesini N, Luo S, Rodrigues CO, Moreno SN, Docampo R, 2000. Acidocalcisomes and a vacuolar H+-pyrophosphatase in malaria parasites. Biochem J 347 : 243–253.
  23. Stojdl DF, Clarke MW, 1996. Trypanosoma brucei: analysis of cytoplasmic Ca2+ during differentiation of bloodstream stages in vitro. Exp Parasitol 83 : 134–146.
  24. Uhlemann AC, Cameron A, Eckstein-Ludwig U, Fischbarg J, Iserovich P, Zuniga FA, East M, Lee A, Brady L, Haynes RK, Krishna S, 2005. A single amino acid residue can determine the sensitivity of SERCAs to artemisinins. Nat Struct Mol Biol 12 : 628–629.
  25. Eko FO, Lubitz W, McMillan L, Ramey K, Moore TT, Ananaba GA, Lyn D, Black CM, Igietseme JU, 2003. Recombinant Vibrio cholerae ghosts as a delivery vehicle for vaccinating against Chlamydia trachomatis. Vaccine 21 : 1694–1703.
  26. Gomes YM, Carvalho AB, Santos ML, Cavalcanti VM, Monjour L, 1992. Isolation of Trypanosoma cruzi from blood by histopaque and continuous percoll gradient centrifugations. Appl Biochem Biotechnol 33 : 183–192.
  27. Alonso G, Guevara P, Ramirez JL, 1992. Trypanosomatidae codon usage and GC distribution. Mem Inst Oswaldo Cruz 87 : 517–523.
  28. Fagan MJ, Saier MH Jr, 1994. P-type ATPases of eukaryotes and bacteria: sequence analyses and construction of phylogenetic trees. J Mol Evol 38 : 57–99.
  29. Moller JV, Juul B, Le Maire M, 1996. Structural organization, ion transport, and energy transduction of P-type ATPases. Biochim Biophys Acta 1286 : 1–51.
  30. Deflorin J, Rudolf M, Seebeck T, 1994. The major components of the paraflagellar rod of Trypanosoma brucei are two similar, but distinct proteins which are encoded by two different gene loci. J Biol Chem 269 : 28745–28751.
  31. Trebak M, Chong JM, Herlyn D, Speicher DW, 1999. Efficient laboratory-scale production of monoclonal antibodies using membrane-based high-density cell culture technology. J Immunol Methods 230 : 59–70.
  32. Stiles JK, Meade JC, Kucerova Z, Lyn D, Thompson W, Zakeri Z, Whittaker J, 2001. Trypanosoma brucei infection induces apoptosis and up-regulates neuroleukin expression in the cerebellum. Ann Trop Med Parasitol 95 : 797–810.
  33. Thompson WE, Powell JM, Whittaker JA, Sridaran R, Thomas KH, 1999. Immunolocalization and expression of prohibitin, a mitochondrial associated protein within the rat ovaries. Anat Rec 256 : 40–48.
  34. Thompson WE, Branch A, Whittaker JA, Lyn D, Zilberstein M, Mayo KE, Thomas K, 2001. Characterization of prohibitin in a newly established rat ovarian granulosa cell line. Endocrinology 142 : 4076–4085.
  35. Szostak M, Wanner G, Lubitz W, 1990. Recombinant bacterial ghosts as vaccines. Res Microbiol 141 : 1005–1007.
  36. Eko FO, Witte A, Huter V, Kuen B, Furst-Ladani S, Haslberger A, Katinger A, Hensel A, Szostak MP, Resch S, Mader H, Raza P, Brand E, Marchart J, Jechlinger W, Haidinger W, Lubitz W, 1999. New strategies for combination vaccines based on the extended recombinant bacterial ghost system. Vaccine 17 : 1643–1649.
  37. Eko FO, Szostak MP, Wanner G, Lubitz W, 1994. Production of Vibrio cholerae ghosts (VCG) by expression of a cloned phage lysis gene: potential for vaccine development. Vaccine 12 : 1231–1237.
  38. Mermod N, Ramos JL, Lehrbach PR, Timmis KN, 1986. Vector for regulated expression of cloned genes in a wide range of gram-negative bacteria. J Bacteriol 167 : 447–454.
  39. Eko FO, Hensel A, Bunka S, Lubitz W, 1994. Immunogenicity of Vibrio cholerae ghosts following intraperitoneal immunization of mice. Vaccine 12 : 1330–1334.
  40. Duleu S, Vincendeau P, Courtois P, Semballa S, Lagroye I, Daulouede S, Boucher JL, Wilson KT, Veyret B, Gobert AP, 2004. Mouse strain susceptibility to trypanosome infection: an arginase-dependent effect. J Immunol 172 : 6298–6303.
  41. Igietseme JU, Uriri IM, Kumar SN, Ananaba GA, Ojior OO, Momodu IA, Candal DH, Black CM, 1998. Route of infection that induces a high intensity of gamma interferon-secreting T cells in the genital tract produces optimal protection against Chlamydia trachomatis infection in mice. Infect Immun 66 : 4030–4035.
  42. Bonay P, Duran-Chica I, Fresno M, Alarcon B, Alcina A, 1998. Antiparasitic effects of the intra-Golgi transport inhibitor meg-alomicin. Antimicrob Agents Chemother 42 : 2668–2673.
  43. Harris TH, Mansfield JM, Paulnock DM, 2007. CpG oligodeoxy-nucleotide treatment enhances innate resistance and acquired immunity to African trypanosomes. Infect Immun 75 : 2366–2373.
  44. Pays E, Vanhamme L, Perez-Morga D, 2004. Antigenic variation in Trypanosoma brucei: facts, challenges and mysteries. Curr Opin Microbiol 7 : 369–374.
  45. McCulloch R, 2004. Antigenic variation in African trypanosomes: monitoring progress. Trends Parasitol 20 : 117–121.
  46. Mkunza F, Olaho WM, Powell CN, 1995. Partial protection against natural trypanosomiasis after vaccination with a flagellar pocket antigen from Trypanosoma brucei rhodesiense. Vaccine 13 : 151–154.
  47. Luhrs KA, Fouts DL, Manning JE, 2003. Immunization with recombinant paraflagellar rod protein induces protective immunity against Trypanosoma cruzi infection. Vaccine 21 : 3058–3069.
  48. Magez S, Lucas R, Darji A, Songa EB, Hamers R, De BP, 1993. Murine tumour necrosis factor plays a protective role during the initial phase of the experimental infection with Trypanosoma brucei brucei. Parasite Immunol 15 : 635–641.
  49. Magez S, Radwanska M, Beschin A, Sekikawa K, De BP, 1999. Tumor necrosis factor alpha is a key mediator in the regulation of experimental Trypanosoma brucei infections. Infect Immun 67 : 3128–3132.
  50. Uzonna JE, Kaushik RS, Gordon JR, Tabel H, 1999. Cytokines and antibody responses during Trypanosoma congolense infections in two inbred mouse strains that differ in resistance. Parasite Immunol 21 : 57–71.
  51. Hertz CJ, Filutowicz H, Mansfield JM, 1998. Resistance to the African trypanosomes is IFN-gamma dependent. J Immunol 161 : 6775–6783.
  52. Radwanska M, Guirnalda P, De TC, Ryffel B, Black S, Magez S, 2008. Trypanosomiasis-induced B cell apoptosis results in loss of protective anti-parasite antibody responses and abolishment of vaccine-induced memory responses. PLoS Pathol 4 : e1000078.
  53. Radwanska M, Magez S, Dumont N, Pays A, Nolan D, Pays E, 2000. Antibodies raised against the flagellar pocket fraction of Trypanosoma brucei preferentially recognize HSP60 in cDNA expression library. Parasite Immunol 22 : 639–650.
  54. Shi M, Wei G, Pan W, Tabel H, 2006. Experimental African trypanosomiasis: a subset of pathogenic, IFN-gamma-producing, MHC class II-restricted CD4+ T cells mediates early mortality in highly susceptible mice. J Immunol 176 : 1724–1732.
  55. Namangala B, Noel W, De BP, Brys L, Beschin A, 2001. Relative contribution of interferon-gamma and interleukin-10 to resistance to murine African trypanosomosis. J Infect Dis 183 : 1794–1800.
  56. Bakhiet M, Olsson T, Edlund C, Hojeberg B, Holmberg K, Lorentzen J, Kristensson K, 1993. A Trypanosoma brucei brucei-derived factor that triggers CD8+ lymphocytes to interferon-gamma secretion: purification, characterization and protective effects in vivo by treatment with a monoclonal antibody against the factor. Scand J Immunol 37 : 165–178.
  57. Bakhiet M, Olsson T, Mhlanga J, Buscher P, Lycke N, van der Meide PH, Kristensson K, 1996. Human and rodent interferon-gamma as a growth factor for Trypanosoma brucei. Eur J Immunol 26 : 1359–1364.
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2009.81.407
Loading
/content/journals/10.4269/ajtmh.2009.81.407
Loading

Data & Media loading...

  • Received : 25 Jan 2008
  • Accepted : 23 May 2009

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error