NDLI: Human Defensin α-1 Causes Trypanosoma cruzi Membrane Pore Formation and Induces DNA Fragmentation, Which Leads to Trypanosome Destruction▿

Content Provider	PubMed Central
Author	Madison, M. Nia Kleshchenko, Yuliya Y. Nde, Pius N. Simmons, Kaneatra J. Lima, Maria F. Villalta, Fernando
Copyright Year	2007
Abstract	Human defensins play a fundamental role in the initiation of innate immune responses to some microbial pathogens. Here we show that human defensin α-1 displays a trypanocidal role against Trypanosoma cruzi, the causative agent of Chagas' disease. The toxicity of human defensin α-1 against T. cruzi is mediated by membrane pore formation and the induction of nuclear and mitochondrial DNA fragmentation, leading to trypanosome destruction. Exposure of trypomastigote and amastigote forms of T. cruzi to defensin α-1 significantly reduced parasite viability in a peptide concentration-dependent and saturable manner. The toxicity of defensin α-1 against T. cruzi is blocked by anti-defensin α-1 immunoglobulin G. Electron microscopic analysis of trypomastigotes exposed to defensin α-1 revealed pore formation in the cellular and flagellar membranes, membrane disorganization, and blebbing as well as cytoplasmic vacuolization. Furthermore, human defensin α-1 enters the trypanosome when membrane pores are present and is associated with later intracellular damage. Trypanosome membrane depolarization abolished the toxicity of defensin α-1 against the parasite. Preincubation of trypomastigotes with defensin α-1 followed by exposure to human epithelial cells significantly reduced T. cruzi infection in these cells. Thus, human defensin α-1 is an innate immune molecule that causes severe toxicity to T. cruzi and plays an important role in reducing cellular infection. This is the first report showing that human defensin α-1 causes membrane pore formation in a human parasite, leading to trypanosome destruction.
Related Links	http://dx.doi.org/10.1128/iai.00557-07
Ending Page	4791
Page Count	12
Starting Page	4780
File Format	PDF
ISSN	00199567
e-ISSN	10985522
Journal	Infection and Immunity
Issue Number	10
Volume Number	75
Language	English
Publisher	American Society for Microbiology
Publisher Date	2007-10-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Immunology Microbiology Parasitology Infectious Diseases Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Parasitology Immunology Microbiology

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