Androgens Exert a Cysticidal Effect upon Taenia crassiceps by Disrupting Flame Cell Morphology and Function.

Javier R Ambrosio,Laura Valverde-Islas,Lenin Dominguez-Ramírez,Azucena Ruíz-Rosado,Galileo Escobedo,Jorge Morales-Montor,Karen E Nava-Castro,Olivia Reynoso-Ducoing,M Isabel Palacios- Arreola,Pedro Ostoa-Saloma,Bin He

doi:10.1371/journal.pone.0127928

Javier R Ambrosio, Laura Valverde-Islas + Show 9 more

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https://doi.org/10.1371/journal.pone.0127928

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Abstract

The effects of testosterone (T4) and dihydrotestosterone (DHT) on the survival of the helminth cestode parasite Taenia crassiceps, as well as their effects on actin, tubulin and myosin expression and their assembly into the excretory system of flame cells are described in this paper. In vitro evaluations on parasite viability, flow cytometry, confocal microscopy, video-microscopy of live flame cells, and docking experiments of androgens interacting with actin, tubulin, and myosin were conducted. Our results show that T4 and DHT reduce T. crassiceps viability in a dose- and time-dependent fashion, reaching 90% of mortality at the highest dose used (40 ng/ml) and time exposed (10 days) in culture. Androgen treatment does not induce differences in the specific expression pattern of actin, tubulin, and myosin isoforms as compared with control parasites. Confocal microscopy demonstrated a strong disruption of the parasite tegument, with reduced assembly, shape, and motion of flame cells. Docking experiments show that androgens are capable of affecting parasite survival and flame cell morphology by directly interacting with actin, tubulin and myosin without altering their protein expression pattern. We show that both T4 and DHT are able to bind actin, tubulin, and myosin affecting their assembly and causing parasite intoxication due to impairment of flame cell function. Live flame cell video microscopy showing a reduced motion as well changes in the shape of flame cells are also shown. In summary, T4 and DHT directly act on T. crassiceps cysticerci through altering parasite survival as well as the assembly and function of flame cells.

Highlights

Sex hormones affect the course of helminth infection [1, 2], in the case of the cestodes Taenia crassiceps and Taenia solium [3, 4]
We demonstrated by ultrastructural morphology, immunofluorescence, immunochemistry and flow cytometry analysis, that T4 and DHT do not affect the distribution and expression of actin, myosin and tubulin isotypes in tegumental tissues
Our study shows that androgens act directly upon T. crassiceps cysticerci viability without needing the host’s participation: T4 and DHT lead to the irreversible cellular damage of cysticerci

Summary

Introduction

Sex hormones affect the course of helminth infection [1, 2], in the case of the cestodes Taenia crassiceps and Taenia solium [3, 4]. It has been suggested that T. crassiceps can exploit the hormonal microenvironment within the host by a system of trans-regulation, in which the parasite exploits host hormones and growth factors to facilitate infection and potentially increase growth and reproduction rates [5]. Endocrine factors, such as sex or age, are well recognized to be involved in the nature of the immune response to parasites [6] or in the direct effect on them [5]. It has been found that in vitro treatment with progesterone increases T. solium scolex evagination and worm growth in a concentration-independent fashion [10]

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