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Identification and characterization of extracellular vesicles from red cells infected with Babesia divergens and Babesia microti

Babesiosis is a zoonosis and an important blood-borne human parasitic infection that has gained attention because of its growing infection rate in humans by transfer from animal reservoirs. Babesia represents a potential threat to the blood supply because asymptomatic infections in man are common, a...

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Autores principales: Beri, Divya, Rodriguez, Marilis, Singh, Manpreet, Liu, Yunfeng, Rasquinha, Giselle, An, Xiuli, Yazdanbakhsh, Karina, Lobo, Cheryl A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585353/
https://www.ncbi.nlm.nih.gov/pubmed/36275032
http://dx.doi.org/10.3389/fcimb.2022.962944
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author Beri, Divya
Rodriguez, Marilis
Singh, Manpreet
Liu, Yunfeng
Rasquinha, Giselle
An, Xiuli
Yazdanbakhsh, Karina
Lobo, Cheryl A.
author_facet Beri, Divya
Rodriguez, Marilis
Singh, Manpreet
Liu, Yunfeng
Rasquinha, Giselle
An, Xiuli
Yazdanbakhsh, Karina
Lobo, Cheryl A.
author_sort Beri, Divya
collection PubMed
description Babesiosis is a zoonosis and an important blood-borne human parasitic infection that has gained attention because of its growing infection rate in humans by transfer from animal reservoirs. Babesia represents a potential threat to the blood supply because asymptomatic infections in man are common, and blood from such donors can cause severe disease in certain recipients. Extracellular vesicles (EVs) are vesicles released by cells that contain a complex mixture of proteins, lipids, glycans, and genetic information that have been shown to play important roles in disease pathogenesis and susceptibility, as well as cell–cell communication and immune responses. In this article, we report on the identification and characterization of EVs released from red blood cells (RBCs) infected by two major human Babesia species—Babesia divergens from in vitro culture and those from an in vivo B. microti mouse infection. Using nanoparticle tracking analysis, we show that there is a range of vesicle sizes from 30 to 1,000 nm, emanating from the Babesia-infected RBC. The study of these EVs in the context of hemoparasite infection is complicated by the fact that both the parasite and the host RBC make and release vesicles into the extracellular environment. However, the EV frequency is 2- to 10-fold higher in Babesia-infected RBCs than uninfected RBCs, depending on levels of parasitemia. Using parasite-specific markers, we were able to show that ~50%–60% of all EVs contained parasite-specific markers on their surface and thus may represent the specific proportion of EVs released by infected RBCs within the EV population. Western blot analysis on purified EVs from both in vivo and in vitro infections revealed several parasite proteins that were targets of the host immune response. In addition, microRNA analysis showed that infected RBC EVs have different microRNA signature from uninfected RBC EVs, indicating a potential role as disease biomarkers. Finally, EVs were internalized by other RBCs in culture, implicating a potential role for these vesicles in cellular communication. Overall, our study points to the multiple functional implications of EVs in Babesia–host interactions and support the potential that EVs have as agents in disease pathogenesis.
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spelling pubmed-95853532022-10-22 Identification and characterization of extracellular vesicles from red cells infected with Babesia divergens and Babesia microti Beri, Divya Rodriguez, Marilis Singh, Manpreet Liu, Yunfeng Rasquinha, Giselle An, Xiuli Yazdanbakhsh, Karina Lobo, Cheryl A. Front Cell Infect Microbiol Cellular and Infection Microbiology Babesiosis is a zoonosis and an important blood-borne human parasitic infection that has gained attention because of its growing infection rate in humans by transfer from animal reservoirs. Babesia represents a potential threat to the blood supply because asymptomatic infections in man are common, and blood from such donors can cause severe disease in certain recipients. Extracellular vesicles (EVs) are vesicles released by cells that contain a complex mixture of proteins, lipids, glycans, and genetic information that have been shown to play important roles in disease pathogenesis and susceptibility, as well as cell–cell communication and immune responses. In this article, we report on the identification and characterization of EVs released from red blood cells (RBCs) infected by two major human Babesia species—Babesia divergens from in vitro culture and those from an in vivo B. microti mouse infection. Using nanoparticle tracking analysis, we show that there is a range of vesicle sizes from 30 to 1,000 nm, emanating from the Babesia-infected RBC. The study of these EVs in the context of hemoparasite infection is complicated by the fact that both the parasite and the host RBC make and release vesicles into the extracellular environment. However, the EV frequency is 2- to 10-fold higher in Babesia-infected RBCs than uninfected RBCs, depending on levels of parasitemia. Using parasite-specific markers, we were able to show that ~50%–60% of all EVs contained parasite-specific markers on their surface and thus may represent the specific proportion of EVs released by infected RBCs within the EV population. Western blot analysis on purified EVs from both in vivo and in vitro infections revealed several parasite proteins that were targets of the host immune response. In addition, microRNA analysis showed that infected RBC EVs have different microRNA signature from uninfected RBC EVs, indicating a potential role as disease biomarkers. Finally, EVs were internalized by other RBCs in culture, implicating a potential role for these vesicles in cellular communication. Overall, our study points to the multiple functional implications of EVs in Babesia–host interactions and support the potential that EVs have as agents in disease pathogenesis. Frontiers Media S.A. 2022-10-07 /pmc/articles/PMC9585353/ /pubmed/36275032 http://dx.doi.org/10.3389/fcimb.2022.962944 Text en Copyright © 2022 Beri, Rodriguez, Singh, Liu, Rasquinha, An, Yazdanbakhsh and Lobo https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Beri, Divya
Rodriguez, Marilis
Singh, Manpreet
Liu, Yunfeng
Rasquinha, Giselle
An, Xiuli
Yazdanbakhsh, Karina
Lobo, Cheryl A.
Identification and characterization of extracellular vesicles from red cells infected with Babesia divergens and Babesia microti
title Identification and characterization of extracellular vesicles from red cells infected with Babesia divergens and Babesia microti
title_full Identification and characterization of extracellular vesicles from red cells infected with Babesia divergens and Babesia microti
title_fullStr Identification and characterization of extracellular vesicles from red cells infected with Babesia divergens and Babesia microti
title_full_unstemmed Identification and characterization of extracellular vesicles from red cells infected with Babesia divergens and Babesia microti
title_short Identification and characterization of extracellular vesicles from red cells infected with Babesia divergens and Babesia microti
title_sort identification and characterization of extracellular vesicles from red cells infected with babesia divergens and babesia microti
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585353/
https://www.ncbi.nlm.nih.gov/pubmed/36275032
http://dx.doi.org/10.3389/fcimb.2022.962944
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