Exosome secretion affects social motility in Trypanosoma brucei
Autor: | Hiba Waldman Ben-Asher, Lior Binder, Shulamit Michaeli, Gil Arvatz, Vaibhav Chikne, Uthman Okalang, Dror Eliaz, Sriram Kannan, Hadassa Shaked, Smadar Cohen-Chalamish, Itai Dov Tkacz |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Physiology Pathogenesis Exosomes Pathology and Laboratory Medicine Biochemistry Medicine and Health Sciences Image Processing Computer-Assisted Small nucleolar RNAs lcsh:QH301-705.5 In Situ Hybridization Fluorescence Protozoans biology Cell biology Nucleic acids Host-Pathogen Interactions Cellular Structures and Organelles Research Article lcsh:Immunologic diseases. Allergy Trypanosoma Endosome Trypanosoma brucei brucei 030106 microbiology Immunology Motility Trypanosoma brucei Time-Lapse Imaging Microbiology Exosome ESCRT Cell Line 03 medical and health sciences Extraction techniques Virology Parasitic Diseases Genetics Secretion Vesicles Non-coding RNA Molecular Biology Organisms Biology and Life Sciences RNA Cell Biology Blotting Northern biology.organism_classification RNA extraction Parasitic Protozoans Microvesicles Gene regulation Research and analysis methods Microscopy Electron 030104 developmental biology lcsh:Biology (General) Parasitology Gene expression Physiological Processes lcsh:RC581-607 Trypanosoma Brucei Gambiense |
Zdroj: | PLoS Pathogens, Vol 13, Iss 3, p e1006245 (2017) PLoS Pathogens |
ISSN: | 1553-7374 1553-7366 |
Popis: | Extracellular vesicles (EV) secreted by pathogens function in a variety of biological processes. Here, we demonstrate that in the protozoan parasite Trypanosoma brucei, exosome secretion is induced by stress that affects trans-splicing. Following perturbations in biogenesis of spliced leader RNA, which donates its spliced leader (SL) exon to all mRNAs, or after heat-shock, the SL RNA is exported to the cytoplasm and forms distinct granules, which are then secreted by exosomes. The exosomes are formed in multivesicular bodies (MVB) utilizing the endosomal sorting complexes required for transport (ESCRT), through a mechanism similar to microRNA secretion in mammalian cells. Silencing of the ESCRT factor, Vps36, compromised exosome secretion but not the secretion of vesicles derived from nanotubes. The exosomes enter recipient trypanosome cells. Time-lapse microscopy demonstrated that cells secreting exosomes or purified intact exosomes affect social motility (SoMo). This study demonstrates that exosomes are delivered to trypanosome cells and can change their migration. Exosomes are used to transmit stress signals for communication between parasites. Author summary Trypanosomes are the causative agent of major parasitic diseases such as African sleeping sickness, leishmaniosis and Chagas' disease that affect millions of people. These parasites cycle between an insect and a mammalian host. Communication between the parasites and the host must be essential for executing a productive infection and for cycling of the parasite between its hosts. Exosomes are 40-100nm vesicles of endocytic origin, and were shown to affect a variety of biological processes and human diseases. Exosomes were also shown to help pathogens evade the immune system. In this study, we demonstrate that exosomes are secreted from Trypanosoma brucei parasites when trans-splicing is inhibited. These exosomes contain, among many other constituents, a type of RNA known as spliced leader RNA (SL RNA), which is essential in these parasites for formation of all mature mRNA. These exosomes are able to enter neighboring trypanosomes, and only intact exosomes affect the social motility of these parasites. We propose that exosomes can potentially control parasite migration in the insect host by acting as a repellent that drives the fit parasites away from either damaged cells or an unfavorable environment. This mechanism could secure a productive infection. |
Databáze: | OpenAIRE |
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