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

Abstract：

:Human defensins play a fundamental role in the initiation of innate immune responses to some microbial pathogens. Here we show that colonic epithelial model HCT116 cells respond to Trypanosoma cruzi infection by secreting defensin α-1, which reduces infection. We also report the early effects of defensin α-1 on invasive trypomastigotes that involve damage of the flagellar structure to inhibit parasite motility and reduce cellular infection. Short exposure of defensin α-1 to trypomastigotes shows that defensin α-1 binds to the flagellum, resulting in flagellar membrane and axoneme alterations, followed by breaking of the flagellar membrane connected to the trypanosome body, leading to detachment and release of the parasite flagellum. In addition, defensin α-1 induces a significant reduction in parasite motility in a peptide concentration-dependent manner, which is abrogated by anti-defensin α-1 IgG. Preincubation of trypomastigotes with a concentration of defensin α-1 that inhibits 50% trypanosome motility significantly reduced cellular infection by 80%. Thus, human defensin α-1 is an innate immune molecule that is secreted by HCT116 cells in response to T. cruzi infection, inhibits T. cruzi motility, and plays an important role in reducing cellular infection. This is the first report showing a novel cellular innate immune response to a human parasite by secretion of defensin α-1, which neutralizes the motility of a human parasite to reduce cellular infection. The mode of activity of human defensin α-1 against T. cruzi and its function may provide insights for the development of new antiparasitic strategies.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Johnson CA,Rachakonda G,Kleshchenko YY,Nde PN,Madison MN,Pratap S,Cardenas TC,Taylor C,Lima MF,Villalta F

doi

10.1128/IAI.01459-12

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

4139-48

issue

eissn

0019-9567

issn

1098-5522

pii

IAI.01459-12

journal_volume

pub_type

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