Cellular response to trypanosoma cruzi infection induces secretion of defensin α-1, which damages the flagellum, neutralizes trypanosome motility, and inhibits infection

Infection and Immunity

Volumn 81, Issue 11, 2013, Pages 4139-4148

  Johnson, Candice A ^a   Rachakonda, Girish ^a   Kleshchenko, Yuliya Y ^a   Nde, Pius N ^a   Madison, M Nia ^a   Pratap, Siddharth ^a   Cardenas, Tatiana C ^a   Taylor, Chase ^a   Lima, Maria F ^a   Villalta, Fernando ^a  

^a MEHARRY MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA DEFENSIN;

ARTICLE; CONTROLLED STUDY; EPITHELIUM CELL; FLAGELLUM; HUMAN; HUMAN CELL; INNATE IMMUNITY; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN SECRETION; TRYPANOSOMA CRUZI; TRYPANOSOMIASIS; TRYPOMASTIGOTE;

ALPHA-DEFENSINS; CELL MEMBRANE; EPITHELIAL CELLS; FLAGELLA; HCT116 CELLS; HUMANS; LOCOMOTION; TRYPANOSOMA CRUZI;

EID: 84886770691     PISSN: 00199567     EISSN: 10985522     Source Type: Journal    
DOI: 10.1128/IAI.01459-12     Document Type: Article

References (50)

1. Coura JR, Vinas PA. 2010. Chagas disease: a new worldwide challenge. Nature 465:S6-S7. doi:10.1038/nature09221.
2. Tanowitz HB, Weiss LM, Montgomery SP. 2011. Chagas disease has now gone global. PLoS Negl. Trop. Dis. 5:e1136. doi:10.1371/journal.pntd .0001136.
3. Clayton J. 2010. Chagas disease: pushing through the pipeline. Nature 465:S12-S15. doi:10.1038/nature09224.
4. Leslie M. 2011. Infectious diseases. Drug developers finally take aim at a neglected disease. Science 333:933-935.
5. Dobish MC, Villalta F, Waterman MR, Lepesheva GI, Johnston JN. 2012. Organocatalytic, enantioselective synthesis of VNI: a robust therapeutic development platform for Chagas, a neglected tropical disease. Org. Lett. 14:6322-6325.
6. Lepesheva GI, Ott RD, Hargrove TY, Kleshchenko YY, Schuster I, Nes WD, Hill GC, Villalta F, Waterman MR. 2007. Sterol 14αdemethylase as a potential target for antitrypanosomal therapy: enzyme inhibition and parasite cell growth. Chem. Biol. 14:1283-1293.
7. Lepesheva GI, Park HW, Hargrove TY, Vanhollebeke B, Wawrzak Z, Harp JM, Sundaramoorthy M, Nes WD, Pays E, Chaudhuri M, Villalta F, Waterman MR. 2010. Structural insights into inhibition of sterol- 14alpha-demethylase in the human pathogen Trypanosoma cruzi. J. Biol. Chem. 285:25582-25590.
8. Lepesheva GI, Villalta F, Waterman MR. 2011. Targeting Trypanosoma cruzi sterol 14αdemethylase (CYP51). Adv. Parasitol. 75:65-87.
9. Villalta F, Dobish MC, Nde PN, Kleshchenko YY, Hargrove TY, Johnson CA, Waterman MR, Johnston JN, Lepesheva GI. 2013. VNI cures the acute and chronic experimental Chagas disease. J. Infect. Dis. 208: 504-511.
10. Pinazo MJ, Espinosa G, Gállego M, López-Chejade PL, Urbina JA, Gascón J. 2010. Successful treatment with posaconazole of a patient with chronic Chagas disease and systemic lupus erythematosus. Am. J. Trop. Med. Hyg. 82:583-587.
11. Garg N, Bhatia V. 2005. Current status and future prospects for a vaccine against American trypanosomiasis. Expert Rev. Vaccines 4:867-880.
12. Fischer E, Ouaissi MA, Velge P, Cornette J, Kazatchkine MD. 1988. gp 58168, a parasite component that contributes to the escape of the trypomastigote form of T. cruzi from damage by the human alternative complement pathway. Immunology 65:299-303.
13. Cunliffe RN, Kamal M, Rose FR, James PD, Mahida YR. 2002. Expression of antimicrobial neutrophil defensins in epithelial cells of active inflammatory bowel disease mucosa. J. Clin. Pathol. 55:298-304.
14. Ganz T. 2003. Defensins: antimicrobial peptides of innate immunity. Nat. Rev. Immunol. 3:710-720.
15. Lehrer RI, Lu W. 2012. αDefensins in human innate immunity. Immunol. Rev. 245:84-112.
16. Ouellette AJ, Selsted ME. 1996. Paneth cells defensins: endogenous peptide components of intestinal host defense. FASEB J. 10:1280-1289.
17. Selsted ME, Ouellette AJ. 2005. Mammalian defensins in the antimicrobial immune response. Nat. Immunol. 6:551-557.
18. Yang D, Biragyn A, Kwak LW, Oppenheim JJ. 2002. Mammalian defensins in immunity: more than just microbicidal. Trends Immunol. 23: 291-296.
19. Klotman ME, Chang TL. 2006. Defensins in innate antiviral immunity. Nat. Rev. Immunol. 6:447-456.
20. Ganz T, Lehrer RI. 1998. Antimicrobial peptides of vertebrates. Curr. Opin. Immunol. 10:41-44.
21. Agerberth B, Charo J, Werr J, Olsson B, Idali F, Lindbom L, Kiessling R, Jörnvall H, Wigzell H, Gudmundsson GH. 2000. The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood 96:3086-3093.
22. Dugan AS, Maginnis MS, Jordan JA, Gasparovic ML, Manley K, Page R, Williams G, Porter E, O'Hara BA, Atwood WJ. 2008. Human alphadefensin inhibit BK virus infection by aggregating virions and blocking binding to host cells. J. Biol. Chem. 283:31125-31132.
23. Menendez A, Finlay BB. 2007. Defensins in the immunology of bacterial infections. Curr. Opin. Immunol. 19:385-391.
24. Smith JG, Nemerow GR. 2008. Mechanism of adenovirus neutralization by human α defensins. Cell Host Microbe 3:11-19.
25. Mor A. 2009. Multifunctional host defense peptides: antiparasitic activities. FEBS J. 276:6474-6482.
26. Lehrer RI, Lichtenstein AK, Ganz T. 1993. Defensins: antimicrobial and cytotoxic peptides of mammalian cells. Annu. Rev. Immunol. 11:105-128.
27. Lehrer RI. 2007. Multispecific myeloid defensins. Curr. Opin. Hematol. 14:16-21.
28. Yamamoto-Furusho JK, Barnich N, Hisamatsu T, Podolsky DK. 2010. MDP-NOD2 stimulation induces HNP-1 secretion which contributes to NOD2 anti-bacterial function. Inflamm. Bowel Dis. 16:736-742.
29. Lima MF, Villalta F. 1989. Trypanosoma cruzi trypomastigote clones differentially express a parasite cell adhesion molecule. Mol. Biochem. Parasitol. 33:159-170.
30. Johnson CA, Kleshchenko YY, Ikejiani AO, Udoko AN, Cardenas TC, Pratap S, Duquette MA, Lima MF, Lawler J, Villalta F, Nde PN. 2012. Thrombospondin-1 interacts with Trypanosoma cruzi surface calreticulin to enhance cellular infection. PLoS One 7:e40614. doi:10.1371/journal .pone.0040614.
31. Daher KA, Lehrer RI, Ganz T, Kronenberg M. 1988. Isolation and characterization of human defensin cDNA clones. Proc. Natl. Acad. Sci. U. S. A. 85:7327-7331.
32. Valore EV, Ganz T. 1992. Posttranslational processing of defensins in immature human myeloid cells. Blood 79:1538-1544.
33. Nde PN, Simmons KJ, Kleshchenko YY, Pratap S, Lima MF, Villalta F. 2006. Silencing of the laminin gamma-1 gene blocks Trypanosoma cruzi infection. Infect. Immun. 74:1643-1648.
34. Simmons KJ, Nde PN, Kleshchenko YY, Lima MF, Villalta F. 2006. Stable RNA interference of host thrombospondin-1 blocks Trypanosoma cruzi infection. FEBS Lett. 580:2365-2370.
35. Villalta F, Kierszenbaum F. 1984. Role of inflammatory cells in Chagas' disease. II. Interactions of mouse macrophages and human monocytes with intracellular forms of Trypanosoma cruzi: uptake and mechanism of destruction. J. Immunol. 133:3338-3343.
36. Villalta F, Zhang Y, Bibb KE, Kappes JC, Lima MF. 1998. The cysteinecysteine family of chemokines RANTES, MIP-1alpha, and MIP-1beta in-duce trypanocidal activity in human macrophages via nitric oxide. Infect. Immun. 66:4690-4695.
37. Madison MN, Kleshchenko YY, Nde PN, Simmons KJ, Lima MF, Villalta F. 2007. Human defensin alpha-1 causes Trypanosoma cruzi membrane pore formation and induces DNA fragmentation, which leads to trypanosome destruction. Infect. Immun. 75:4780-4791.
38. Horne RW, Bangham AD, Whittaker VP. 1963. Negatively stained lipoprotein membranes. Nature 200:1340.
39. Villalta F, Kierszenbaum F. 1984. Role of inflammatory cells in Chagas' disease. I. Uptake and mechanism of destruction of intracellular (amastigote) forms of Trypanosoma cruzi by human eosinophils. J. Immunol. 132:2053-2058.
40. Ralston KS, Kabututu ZP, Melehani SH, Oberholzer M, Hill KL. 2009. The Trypanosoma brucei flagellum: moving parasites in new directions. Annu. Rev. Microbiol. 63:335-362.
41. Ashitani J, Mukae H, Nakazato M, Ihi T, Mashimoto H, Kadota J, Kohno S, Matsukura S. 1998. Elevated concentrations of defensins in bronchoalveolar lavage fluid in diffuse panbronchiolitis. Eur. Respir. J. 11:104-111.
42. Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, Lehrer RI. 1985. Defensins: natural peptide antibiotics of human neutrophils. J. Clin. Invest. 76:1427-1435.
43. Kim C, Gajendran N, Mittrücker HW, Weiwad M, Song YH, Hurwitz R, Wilmanns M, Fischer G, Kaufmann SH. 2005. Human alphadefensins neutralize anthrax lethal toxin and protect against its fatal consequences. Proc. Natl. Acad. Sci. U. S. A. 102:4830-4835.
44. Ihi T, Nakazato M, Mukae H, Matsukura S. 1997. Elevated concentrations of human neutrophil peptides in plasma, blood, and body fluids from patients with infections. Clin. Infect. Dis. 25:1134-1140.
45. Panyutich AV, Panyutich EA, Krapivin VA, Baturevich EA, Ganz T. 1993. Plasma defensin concentrations are elevated in patients with septicemia or bacterial meningitis. J. Lab. Clin. Med. 122:202-207.
46. Ashitani J, Nakazato M, Mukae H, Taniguchi H, Date Y, Matsukura S. 2000. Recombinant granulocyte colony-stimulating factor induces production of human neutrophil peptides in lung cancer patients with neutropenia. Regul. Pept. 95:87-92.
47. Mukae H, Iiboshi H, Nakazato M, Hiratsuka T, Tokojima M, Abe K, Ashitani J, Kadota J, Matsukura S, Kohno S. 2002. Raised plasma concentrations of alpha-defensins in patients with idiopathic pulmonary fibrosis. Thorax 57:623-628.
48. Tanaka S, Edberg CJ, Winn C, Fassina G, Kimberley R. 2003. FcγIIIb allele-sensitive release of alpha-defensins: anti-neutrophil cytoplasmic antibody- induced release of chemotaxins. J. Immunol. 171:6090-6096.
49. Zhang Y, Wuyuan L, Hong M. 2010. The membrane-bound structure and topology of a human αdefensin indicate a dimer pore mechanism for membrane disruption. Biochemistry 49:9770-9782.
50. Andreeva-Kovalevskaya ZI, Solonin AS, Sineva EV, Ternovsky VI. 2008. Pore-forming proteins and adaptation of living organisms to environmental conditions. Biochemistry (Mosc.) 73:1473-1492.