Abstract
Human defensins play a fundamental role in the initiation of innate immune responses to some microbial pathogens. In this paper, we show that human α-defensin-5 displays a parasiticidal role against Toxoplasma gondii, the causative agent of toxoplasmosis. Exposure of the tachyzoite form of T. gondii to defensin induced aggregation and significantly reduced parasite viability in a concentration-dependent peptide. Pre-incubation of tachyzoites with human α-defensin-5 followed by exposure to a mouse embryonal cell line (NIH/3T3) significantly reduced T. gondii infection in these cells. Thus, human α-defensin-5 is an innate immune molecule that causes severe toxocity to T. gondii and plays an important role in reducing cellular infection. This is the first report showing that human α-defensin-5 causes aggregation, leading to Toxoplasma destruction.
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs11626-009-9271-9/MediaObjects/11626_2009_9271_Fig1_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs11626-009-9271-9/MediaObjects/11626_2009_9271_Fig2_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs11626-009-9271-9/MediaObjects/11626_2009_9271_Fig3_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs11626-009-9271-9/MediaObjects/11626_2009_9271_Fig4_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs11626-009-9271-9/MediaObjects/11626_2009_9271_Fig5_HTML.gif)
Similar content being viewed by others
References
Aley S. B.; Zimmerman M.; Hetsko M.; Selsted M. E.; Gillin F. D. Killing of Giardia lamblia by cryptins and cationic neutrophil peptides. Infect. Immun. 62: 5397–5403; 1994.
Ayabe T.; Satchell D. P.; Wilson C. L.; Parks W. C.; Selsted M. E.; Ouellette A. J. Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Nat. Immunol. 1: 113–118; 2000.
Boman H. G. Peptide antibodies and their role in innate immunity. Annu. Rev. Immunol. 13: 61–92; 1995.
Brogden K. A. Antimicrobial peptides: Pore formers or metabolic inhibitors in bacteria? Nat. Rev. Microbiol. 3: 238–250; 2005.
Brown K. L.; Hancock R. E. Cationic host defense (antimicrobial) peptides. Curr. Opin. Immunol. 18: 24–30; 2006.
Chen H.; Xu Z.; Peng L.; Fang X.; Yin X.; Xu N.; Cen P. Recent advances in the research and development of human defensins. Peptides 27: 931–940; 2006.
Duits L. A.; Ravensbergen B.; Rademaker M.; Hiemstra P. S.; Nibbering P. H. Expression of beta-defensin 1 and 2 mRNA by human monocytes, macrophages and dendritic cells. Immunology 106: 517–525; 2002.
Ganz T. Defensins: Antimicrobial peptides of innate immunity. Nat. Rev. Immunol. 3: 710–720; 2003.
Hancock R. E.; Sahl H. G. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat. Biotechnol. 24: 1551–1557; 2006.
Hoffmann J. A.; Kafatos F. C.; Janeway C. A.; Ezekowitz R. A. Phylogenetic perspectives in innate immunity. Science 284: 1313–1318; 1999.
Huang L. C.; Redfern R. L.; Narayanan S.; Reins R. Y.; McDermott A. M. In vitro activity of human beta-defensin 2 against Pseudomonas aeruginosa in the presence of tear fluid. Antimicrob. Agents Chemother. 51: 3853–3860; 2007.
Ihi T.; Nakazato M.; Mukae H.; Matsukura S. Elevated concentrations of human neutrophil peptides in plasma, blood, and body fluids from patients with infections. Clin. Infect. Dis. 25: 1134–1140; 1997.
Jones D. E.; Bevins C. L. Paneth cells of the human small intestine express an antimicrobial peptide gene. J. Biol. Chem. 267: 23216–23225; 1992.
Lai Y.; Gallo R. L. AMPed up immunity: How antimicrobial peptides have multiple roles in immune defense. Trends Immunol. 30: 131–141; 2009.
Lehrer R. I.; Ganz T. Antimicrobial peptides in mammalian and insect host defense. Curr. Opin. Immunol. 11: 23–27; 1999.
Liévin-Le Moal V.; Servin A. L. The front line of enteric host defense against unwelcome intrusion of harmful microorganisms: Mucins, antimicrobial peptides, and microbiota. Clin. Microbiol. Rev. 19: 315–337; 2006.
McGwire B. S.; Olson C. L.; Tack B. F.; Engman D. M. Killing of African trypanosomes by antimicrobial peptides. J. Infect. Dis. 188: 146–152; 2003.
Morrison G.; Morrison G.; Kilanowski F.; Davidson D.; Dorin J. Characterization of the mouse beta defensins 1, Defb1, mutant mouse model. Infect. Immun. 70: 3053–3060; 2002.
Moser C.; Weiner D. J.; Lysenko E.; Bals R.; Weiser J. N.; Wilson J. M. beta-Defensin 1 contributes to pulmonary innate immunity in mice. Infect. Immun. 70: 3068–3072; 2002.
Panyutich A. V.; Panyutich E. A.; Krapivin V. A.; Baturevich E. A.; Ganz T. Plasma defensins concentrations are elevated in patients with septicemia or bacterial meningitis. J. Lab. Clin. Med. 122: 202–207; 1993.
Powers J. P.; Hancock R. E. The relationship between peptide structure and antibacterial activity. Peptides 24: 1681–1691; 2003.
Salzman N. H.; Ghosh D.; Huttner K. M.; Paterson Y.; Bevins C. L. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 422: 522–526; 2003.
Striepen B.; He C. Y.; Matrajt M.; Soldati D.; Roos D. S. Expression, selection, and organellar targeting of the green fluorescent protein in Toxoplasma gondii. Mol. Biochem. Parasitol. 1: 325–338; 1998.
Wilson C. L.; Ouellette A. J.; Satchell D. P.; Ayabe T.; López-Boado Y. S.; Stratman J. L.; Hultgren S. J.; Matrisian L. M.; Parks W. C. Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 286: 113–117; 1999.
Wimley W. C.; Selsted M. E.; White S. H. Interactions between human defensins and lipid bilayers: Evidence for formation of multimeric pores. Protein Sci. 3: 1362–1373; 1994.
Acknowledgments
This work was supported by the Bio-oriented Technology Research Advancement Institution (BRAIN) and Grants-in Aid for Scientific Research (A) from the Japan Society for the Promotion of Science (JSPS).
Author information
Authors and Affiliations
Corresponding author
Additional information
Editor: J. Denry Sato
Rights and permissions
About this article
Cite this article
Tanaka, T., Rahman, M.M., Battur, B. et al. Parasiticidal activity of human α-defensin-5 against Toxoplasma gondii . In Vitro Cell.Dev.Biol.-Animal 46, 560–565 (2010). https://doi.org/10.1007/s11626-009-9271-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11626-009-9271-9