Parasites, Hosts and Diseases

The Korea Society for Parasitology and Tropical Medicine (대한기생충학·열대의학회)
권호 표지
DOI QR코드

DOI QR Code

Characterization of Plasmodium berghei Homologues of T-cell Immunomodulatory Protein as a New Potential Candidate for Protecting against Experimental Cerebral Malaria

  • Cui, Ai (Department of Pathogen Biology, College of Basic Medical Sciences, China Medical University) ;
  • Li, Yucen (Department of Pathogen Biology, College of Basic Medical Sciences, China Medical University) ;
  • Zhou, Xia (Department of Pathogen Biology, College of Basic Medical Sciences, China Medical University) ;
  • Wang, Lin (Department of Pathogen Biology, College of Basic Medical Sciences, China Medical University) ;
  • Luo, Enjie (Department of Pathogen Biology, College of Basic Medical Sciences, China Medical University)
  • Received : 2018.10.14
  • Accepted : 2019.04.16
  • Published : 2019.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

The pathogenesis of cerebral malaria is biologically complex and involves multi-factorial mechanisms such as microvascular congestion, immunopathology by the pro-inflammatory cytokine and endothelial dysfunction. Recent data have suggested that a pleiotropic T-cell immunomodulatory protein (TIP) could effectively mediate inflammatory cytokines of mammalian immune response against acute graft-versus-host disease in animal models. In this study, we identified a conserved homologue of TIP in Plasmodium berghei (PbTIP) as a membrane protein in Plasmodium asexual stage. Compared with PBS control group, the pathology of experimental cerebral malaria (ECM) in rPbTIP intravenous injection (i.v.) group was alleviated by the downregulation of pro-inflammatory responses, and rPbTIP i.v. group elicited an expansion of regulatory T-cell response. Therefore, rPbTIP i.v. group displayed less severe brain pathology and feverish mice in rPbTIP i.v. group died from ECM. This study suggested that PbTIP may be a novel promising target to alleviate the severity of ECM.

Keywords

References

  1. World Health Organization. World Malaria Report, 2018. Geneva, Switzerland. World Health Organization. 2018.
  2. White NJ, Pukrittayakamee S, Hien TT, Faiz MA, Mokuolu OA, Dondorp AM. Malaria. Lancet 2014; 383: 723-735. https://doi.org/10.1016/S0140-6736(13)60024-0
  3. John CC, Bangirana P, Byarugaba J, Opoka RO, Idro R, Jurek AM, Wu B, Boivin MJ. Cerebral malaria in children is associated with long-term cognitive impairment. Pediatrics 2008; 122: 92-99. https://doi.org/10.1542/peds.2007-2258
  4. MacCormick IJC, Beare NA, Taylor TE, Barrera V, White VA, Hiscott P, Molyneux ME, Dhillon B, Harding SP. Cerebral malaria in children: using the retina to study the brain. Brain 2014; 137: 2119-2142. https://doi.org/10.1093/brain/awu001
  5. Guo J, Wakninegrinberg JH, Mitchell AJ, Barenholz Y, Golenser J. Reduction of experimental cerebral malaria and its related proinflammatory responses by the novel liposome-based ${\beta}$-methasone nanodrug. Biomed Res Int 2014; 2014: 66-70.
  6. Khandare AV, Bobade D, Deval M, Patil T, Saha B, Prakash D. Expression of negative immune regulatory molecules, pro-inflammatory chemokine and cytokines in immunopathology of ECM developing mice. Acta Trop 2017; 172: 58-63. https://doi.org/10.1016/j.actatropica.2017.04.025
  7. Dunst J, Kamena F, Matuschewski K. Cytokines and Chemokines in Cerebral Malaria Pathogenesis. Front Cell Infect Microbiol 2017; 7: 324. https://doi.org/10.3389/fcimb.2017.00324
  8. Mathieu C, Demarta-Gatsi C, Porcherie A, Brega S, Thiberge S, Ronce K, Smith L, Peronet R, Amino R, Menard R, Mecheri S. Plasmodium berghei histamine-releasing factor favours liver-stage development via inhibition of IL-6 production and associates with a severe outcome of disease. Cell Microbiol 2015; 17: 542-558. https://doi.org/10.1111/cmi.12382
  9. Keita Alassane S, Nicolau-Travers ML, Menard S, Andreoletti O, Cambus JP, Gaudre N, Wlodarczyk M, Blanchard N, Berry A, Abbes S, Colongo D, Faye B, Augereau JM, Lacroux C, Iriart X, Benoit-Vical F. Young Sprague Dawley rats infected by Plasmodium berghei: A relevant experimental model to study cerebral malaria. PLoS One 2017; 12: e0181300. https://doi.org/10.1371/journal.pone.0181300
  10. Pino P, Vouldoukis I, Kolb JP, Mahmoudi N, Desportes-Livage I, Bricaire F, Danis M, Dugas B, Mazier D. Plasmodium falciparum--infected erythrocyte adhesion induces caspase activation and apoptosis in human endothelial cells. J Infect Dis 2003; 187: 1283-1290. https://doi.org/10.1086/373992
  11. Fiscella M, Perry JW, Teng B, Bloom M, Zhang C, Leung K, Pukac L, Florence K, Concepcion A, Liu B, Meng Y, Chen C, Elgin EC, Kanakaraj P, Kaufmann TE, Porter J, Cibotti R, Mei Y, Zhou J, Chen G, Roschke V, Komatsoulis G, Mansfield B, Ruben S, Sanyal I, Migone TS. TIP, a T-cell factor identified using high-throughput screening increases survival in a graft-versus-host disease model. Nat Biotechnol 2003; 21: 302-307. https://doi.org/10.1038/nbt797
  12. Nono JK, Lutz MB, Brehm K. EmTIP, a T-Cell Immunomodulatory Protein Secreted by the Tapeworm Echinococcus multilocularis Is Important for Early Metacestode Development. PLoS Neglect Trop Dis 2014; 8: e2632. https://doi.org/10.1371/journal.pntd.0002632
  13. Blagborough AM, Sinden RE. Plasmodium berghei HAP2 induces strong malaria transmission-blocking immunity in vivo and in vitro. Vaccine 2009; 27: 5187-5194. https://doi.org/10.1016/j.vaccine.2009.06.069
  14. Chan JA, Fowkes FJ, Beeson JG. Surface antigens of Plasmodium falciparum-infected erythrocytes as immune targets and malaria vaccine candidates. Cell Mol Life Sci 2014; 71: 3633-3657. https://doi.org/10.1007/s00018-014-1614-3
  15. Dempsey E, Prudencio M, Fennell BJ, Gomes-Santos CS, Barlow JW, Bell A. Antimitotic herbicides bind to an unidentified site on malarial parasite tubulin and block development of liver-stage Plasmodium parasites. Mol Biochem Parasit 2013; 188: 116-127. https://doi.org/10.1016/j.molbiopara.2013.03.001
  16. Deligianni E, Morgan RN, Bertuccini L, Kooij TW, Laforge A, Nahar C, Poulakakis N, Schuler H, Louis C, Matuschewski K, Siden-Kiamos I. Critical role for a stage-specific actin in male exflagellation of the malaria parasite. Cell Microbiol 2011; 13: 1714-1730. https://doi.org/10.1111/j.1462-5822.2011.01652.x
  17. Eisenhaber B, Maurer-Stroh S, Novatchkova M, Schneider G, Eisenhaber F. Enzymes and auxiliary factors for GPI lipid anchor biosynthesis and post-translational transfer to proteins. Bioessays 2003; 25: 367-385. https://doi.org/10.1002/bies.10254
  18. Baccarella A, Huang BW, Fontana MF, Kim CC. Loss of Toll-like receptor 7 alters cytokine production and protects against experimental cerebral malaria. Malaria J 2014; 13: 354. https://doi.org/10.1186/1475-2875-13-354
  19. He X, Yan J, Zhu X, Wang Q, Pang W, Qi Z, Wang M, Luo E, Parker DM, Cantorna MT, Cui L, Cao Y. Vitamin D inhibits the occurrence of experimental cerebral malaria in mice by suppressing the host inflammatory response. J Immunol 2014; 193: 1314-1323. https://doi.org/10.4049/jimmunol.1400089
  20. Mlambo G, Kumar N, Yoshida S. Functional immunogenicity of baculovirus expressing Pfs25, a human malaria transmission-blocking vaccine candidate antigen. Vaccine 2010; 28: 7025-7029. https://doi.org/10.1016/j.vaccine.2010.08.022
  21. Kumar R, Ray PC, Datta D, Bansal GP, Angov E, Kumar N. Nanovaccines for malaria using Plasmodium falciparum antigen Pfs25 attached gold nanoparticles. Vaccine 2015; 33: 5064-5071. https://doi.org/10.1016/j.vaccine.2015.08.025
  22. Wei X, Li Y, Sun X, Zhu X, Feng Y, Liu J, Jiang Y, Shang H, Cui L, Cao Y. Erythropoietin protects against murine cerebral malaria through actions on host cellular immunity. Infect Immun 2014; 82: 165-173. https://doi.org/10.1128/IAI.00929-13
  23. Yamakuchi M, Kirkiles-Smith NC, Ferlito M, Cameron SJ, Bao C, Fox-Talbot K, Wasowska BA, Baldwin WM 3rd, Pober JS, Lowenstein CJ. Antibody to human leukocyte antigen triggers endothelial exocytosis. Proc Natl Acad Sci USA 2007; 104: 1301-1306. https://doi.org/10.1073/pnas.0602035104
  24. Wahl SM, Vazquez N, Chen W. Regulatory T cells and transcription factors: gatekeepers in allergic inflammation. Curr Opin Immunol 2004; 16: 768-774. https://doi.org/10.1016/j.coi.2004.09.006
  25. Sakaguchi S. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 2004; 22: 531-562. https://doi.org/10.1146/annurev.immunol.21.120601.141122
  26. Sakaguchi S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol 2005; 6: 345-352. https://doi.org/10.1038/ni1178
  27. McHugh RS, Whitters MJ, Piccirillo CA, Young DA, Shevach EM, Collins M, Byrne MC. CD4+CD25+ immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity 2002; 16: 311-323. https://doi.org/10.1016/S1074-7613(02)00280-7
  28. Chen W, Jin W, Wahl S. Engagement of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) induces transforming growth factor ${\beta}$ ($TGF-{\beta}$) production by murine CD4 T Cells. J Exp Med 1998; 188: 1849-1857. https://doi.org/10.1084/jem.188.10.1849
  29. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 2003; 4: 330-336. https://doi.org/10.1038/ni904
  30. Khattri R, Cox T, Yasayko SA, Ramsdell F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol 2003; 4: 337-342. https://doi.org/10.1038/ni909
  31. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003; 299: 1057-1061. https://doi.org/10.1126/science.1079490
  32. Amani V, Vigario AM, Belnoue E, Marussig M, Fonseca L, Mazier D, Renia L. Involvement of IFN-gamma receptor-medicated signaling in pathology and anti-malarial immunity induced by Plasmodium berghei infection. Eur J Immunol 2000; 30: 1646. https://doi.org/10.1002/1521-4141(200006)30:6<1646::AID-IMMU1646>3.0.CO;2-0
  33. Belnoue E, Potter SM, Rosa DS, Mauduit M, Gruner AC, Kayibanda M, Mitchell AJ, Hunt NH, Renia L. Control of pathogenic CD8+ T cell migration to the brain by IFN-gamma during experimental cerebral malaria. Parasite Immunol 2010; 30: 544-553. https://doi.org/10.1111/j.1365-3024.2008.01053.x
  34. Grau GE, Heremans H, Piguet PF, Pointaire P, Lambert PH, Billiau A, Vassalli P. Monoclonal antibody against interferon gamma can prevent experimental cerebral malaria and its associated overproduction of tumor necrosis factor. Proc Natl Acad Sci USA 1989; 86: 5572-5574. https://doi.org/10.1073/pnas.86.14.5572
  35. Turner GD, Morrison H, Jones M, Davis TM, Looareesuwan S, Buley ID, Gatter KC, Newbold CI, Pukritayakamee S, Nagachinta B, White NJ, Berendt AR. An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. Am J Pathol 1994; 145: 1057-1069.
  36. Roberts DJ, Pain A, Kai O, Kortok M, Marsh K. Autoagglutination of malaria-infected red blood cells and malaria severity. Lancet 2000; 355: 1427-1428. https://doi.org/10.1016/S0140-6736(00)02143-7
  37. Renia L, Howland SW, Claser C, Charlotte GA, Suwanarusk R, Hui TT, Russell B, Ng LF. Cerebral malaria: mysteries at the blood-brain barrier. Virulence 2012; 3: 193-201. https://doi.org/10.4161/viru.19013
  38. Medana IM, Turner GD. Human cerebral malaria and the blood-brain barrier. Int J Parasitol 2006; 36: 555-568. https://doi.org/10.1016/j.ijpara.2006.02.004
  39. Turner GD, Ly VC, Nguyen TH, Tran TH, Nguyen HP, Bethell D, Wyllie S, Louwrier K, Fox SB, Gatter KC, Day NP, Tran TH, White NJ, Berendt AR. Systemic endothelial activation occurs in both mild and severe malaria. Correlating dermal microvascular endothelial cell phenotype and soluble cell adhesion molecules with disease severity. Am J Pathol 1998; 152: 1477-1487.
  40. Pain A, Ferguson DJ, Kai O, Urban BC, Lowe B, Marsh K, Roberts DJ. Platelet-mediated clumping of Plasmodium falciparum-infected erythrocytes is a common adhesive phenotype and is associated with severe malaria. Proc Natl Acad Sci USA 2001; 98: 1805-1810. https://doi.org/10.1073/pnas.98.4.1805
  41. Netea MG, Kullberg BJ, Van der Meer JW. Circulating cytokines as mediators of fever. Clin Infect Dis 2000; 31 (suppl): 178-184. https://doi.org/10.1086/317513
  42. Maitland K1, Levin M, English M, Mithwani S, Peshu N, Marsh K, Newton CR. Severe P. falciparum malaria in Kenyan children: evidence for hypovolaemia. QJM 2003; 96: 427-434. https://doi.org/10.1093/qjmed/hcg077
  43. Perkins DJ, Kremsner PG, Weinberg JB. Inverse relationship of plasma prostaglandin E2 and blood mononuclear cell cyclooxygenase-2 with disease severity in children with Plasmodium falciparum malaria. J Infect Dis 2001; 183: 113-118. https://doi.org/10.1086/317660
  44. Schofield L, Hackett F. Signal transduction in host cells by a glycosylphosphatidylinositol toxin of malaria parasites. J Exp Med 1993; 177: 145-153. https://doi.org/10.1084/jem.177.1.145
  45. Olaniyan SA, Amodu OK, Bakare AA, MaritaTroye-Blomberg, Omotade OO, Rockett KA, MalariaGEN Consortium. Tumour necrosis factor alpha promoter polymorphism, TNF -238 is associated with severe clinical outcome of falciparum malaria in Ibadan southwest Nigeria. Acta Trop 2016; 161: 62-67. https://doi.org/10.1016/j.actatropica.2016.05.006
  46. Clark IA, Cowden WB. The pathophysiology of falciparum malaria. Pharmacol Ther 2003; 99: 221-260. https://doi.org/10.1016/S0163-7258(03)00060-3
  47. Grau GE, Taylor TE, Molyneux ME, Wirima JJ, Vassalli P, Hommel M, Lambert PH. Tumor necrosis factor and disease severity in children with falciparum malaria. New Engl J Med 1989; 320: 1586-1591. https://doi.org/10.1056/NEJM198906153202404
  48. Kwiatkowski D, Hill AV, Sambou I, Twumasi P, Castracane J, Manogue KR, Cerami A, Brewster DR, Greenwood BM. TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria. Lancet 1990; 336: 1201-1204. https://doi.org/10.1016/0140-6736(90)92827-5
  49. Perkins DJ, Weinberg JB, Kremsner PG. Reduced interleukin-12 and transforming growth factor-${\beta}1$ in severe childhood malaria: relationship of cytokine balance with disease severity. J Infect Dis 2000; 182: 988-992. https://doi.org/10.1086/315762
  50. Wenisch C, Parschalk B, Burgmann H, Looareesuwan S, Graninger W. Decreased serum levels of TGF-beta in patients with acute Plasmodium falciparum malaria. J Clin Immunol 1995; 15: 69-73. https://doi.org/10.1007/BF01541734
  51. Keswani T, Sarkar S, Sengupta A, Bhattacharyya A. Role of $TGF-{\beta}$ and IL-6 in dendritic cells, Treg and Th17 mediated immune response during experimental cerebral malaria. Cytokine 2016; 88: 154-166. https://doi.org/10.1016/j.cyto.2016.08.034