ArticleInfection and immunity2013
Cellular response to Trypanosoma cruzi infection induces secretion of defensin α-1, which damages the flagellum, neutralizes trypanosome motility, and inhibits infection.
Article in Infection and immunity, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Branched-chain amino acids modulate the proteomic profile of Trypanosoma cruzi metacyclogenesis induced by proline.PLoS neglected tropical diseases · 2024Article
- Trajectory-driven computational analysis for element characterization in Trypanosoma cruzi video microscopy.PloS one · 2024Article
- Antimicrobial Peptides (AMPs): Potential Therapeutic Strategy against Trypanosomiases?Biomolecules · 2023Review
- Motility patterns of Trypanosoma cruzi trypomastigotes correlate with the efficiency of parasite invasion in vitro.Scientific reports · 2020Article
- Sterol 14α-Demethylase Structure-Based Optimization of Drug Candidates for Human Infections with the Protozoan Trypanosomatidae.Journal of medicinal chemistry · 2018Article
- Expression of α-Defensins, CD20+ B-lymphocytes, and Intraepithelial CD3+ T-lymphocytes in the Intestinal Mucosa of Patients with Liver Cirrhosis: Emerging Mediators of Intestinal Barrier Function.Digestive diseases and sciences · 2018Article
- Entamoeba histolytica Alters Ileal Paneth Cell Functions in Intact and Muc2 Mucin Deficiency.Infection and immunity · 2018Article
- Establishment of Larval Zebrafish as an Animal Model to Investigate Trypanosoma cruzi Motility In Vivo.Journal of visualized experiments : JoVE · 2017Article
- Clinical Candidate VT-1161's Antiparasitic Effect In Vitro, Activity in a Murine Model of Chagas Disease, and Structural Characterization in Complex with the Target Enzyme CYP51 from Trypanosoma cruzi.Antimicrobial agents and chemotherapy · 2016Article
- Experimental and Mathematical-Modeling Characterization of Trypanosoma cruzi Epimastigote Motility.PloS one · 2015Article
- Structural basis for rational design of inhibitors targeting Trypanosoma cruzi sterol 14α-demethylase: two regions of the enzyme molecule potentiate its inhibition.Journal of medicinal chemistry · 2014Article
- Immunization with Hexon modified adenoviral vectors integrated with gp83 epitope provides protection against Trypanosoma cruzi infection.PLoS neglected tropical diseases · 2014Article
- Epitope Capsid-Incorporation: New Effective Approach for Vaccine Development for Chagas Disease.Pathogens & immunityArticle
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
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.
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