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Extracellular release of virulence factor major surface protease via exosomes in Leishmania infantum promastigotes

BACKGROUND: The Leishmania spp. protozoa are introduced into humans through a sand fly blood meal, depositing the infectious metacyclic promastigote form of the parasite into human skin. Parasites enter a variety of host cells, although a majority are found in macrophages where they replicate intrac...

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Autores principales: Marshall, Skye, Kelly, Patrick H., Singh, Brajesh K., Pope, R. Marshall, Kim, Peter, Zhanbolat, Bayan, Wilson, Mary E., Yao, Chaoqun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006689/
https://www.ncbi.nlm.nih.gov/pubmed/29921321
http://dx.doi.org/10.1186/s13071-018-2937-y
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author Marshall, Skye
Kelly, Patrick H.
Singh, Brajesh K.
Pope, R. Marshall
Kim, Peter
Zhanbolat, Bayan
Wilson, Mary E.
Yao, Chaoqun
author_facet Marshall, Skye
Kelly, Patrick H.
Singh, Brajesh K.
Pope, R. Marshall
Kim, Peter
Zhanbolat, Bayan
Wilson, Mary E.
Yao, Chaoqun
author_sort Marshall, Skye
collection PubMed
description BACKGROUND: The Leishmania spp. protozoa are introduced into humans through a sand fly blood meal, depositing the infectious metacyclic promastigote form of the parasite into human skin. Parasites enter a variety of host cells, although a majority are found in macrophages where they replicate intracellularly during chronic leishmaniasis. Symptomatic leishmaniasis causes considerable human morbidity in endemic regions. The Leishmania spp. evade host microbicidal mechanisms partially through virulence-associated proteins such as the major surface protease (MSP or GP63), to inactivate immune factors in the host environment. MSP is a metalloprotease encoded by a tandem array of genes belonging to three msp gene classes, whose mRNAs are differentially expressed in different life stages of the parasite. Like other cells, Leishmania spp. release small membrane-bound vesicles called exosomes into their environment. The purpose of this study was to detect MSP proteins in exosomal vesicles of Leishmania spp. protozoa. METHODS: Using mass spectrometry data we determined the profile of MSP class proteins released in L. infantum exosomes derived from promastigotes in their avirulent procyclic (logarithmic) stage and virulent stationary and metacyclic stages. MSP protein isoforms belonging to each of the three msp gene classes could be identified by unique peptides. RESULTS: Metacyclic promastigote exosomes contained the highest, and logarithmic exosomes had the lowest abundance of total MSP. Among the MSP classes, MSPC class had the greatest variety of isoforms, but was least abundant in all exosomes. Nonetheless, all MSP classes were present at higher levels in exosomes released from stationary or metacyclic promastigotes than logarithmic promastigotes. CONCLUSIONS: The data suggest the efficiency of exosome release may be more important than the identity of MSP isoform in determining the MSP content of Leishmania spp. exosomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-018-2937-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-60066892018-06-26 Extracellular release of virulence factor major surface protease via exosomes in Leishmania infantum promastigotes Marshall, Skye Kelly, Patrick H. Singh, Brajesh K. Pope, R. Marshall Kim, Peter Zhanbolat, Bayan Wilson, Mary E. Yao, Chaoqun Parasit Vectors Research BACKGROUND: The Leishmania spp. protozoa are introduced into humans through a sand fly blood meal, depositing the infectious metacyclic promastigote form of the parasite into human skin. Parasites enter a variety of host cells, although a majority are found in macrophages where they replicate intracellularly during chronic leishmaniasis. Symptomatic leishmaniasis causes considerable human morbidity in endemic regions. The Leishmania spp. evade host microbicidal mechanisms partially through virulence-associated proteins such as the major surface protease (MSP or GP63), to inactivate immune factors in the host environment. MSP is a metalloprotease encoded by a tandem array of genes belonging to three msp gene classes, whose mRNAs are differentially expressed in different life stages of the parasite. Like other cells, Leishmania spp. release small membrane-bound vesicles called exosomes into their environment. The purpose of this study was to detect MSP proteins in exosomal vesicles of Leishmania spp. protozoa. METHODS: Using mass spectrometry data we determined the profile of MSP class proteins released in L. infantum exosomes derived from promastigotes in their avirulent procyclic (logarithmic) stage and virulent stationary and metacyclic stages. MSP protein isoforms belonging to each of the three msp gene classes could be identified by unique peptides. RESULTS: Metacyclic promastigote exosomes contained the highest, and logarithmic exosomes had the lowest abundance of total MSP. Among the MSP classes, MSPC class had the greatest variety of isoforms, but was least abundant in all exosomes. Nonetheless, all MSP classes were present at higher levels in exosomes released from stationary or metacyclic promastigotes than logarithmic promastigotes. CONCLUSIONS: The data suggest the efficiency of exosome release may be more important than the identity of MSP isoform in determining the MSP content of Leishmania spp. exosomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-018-2937-y) contains supplementary material, which is available to authorized users. BioMed Central 2018-06-19 /pmc/articles/PMC6006689/ /pubmed/29921321 http://dx.doi.org/10.1186/s13071-018-2937-y Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Marshall, Skye
Kelly, Patrick H.
Singh, Brajesh K.
Pope, R. Marshall
Kim, Peter
Zhanbolat, Bayan
Wilson, Mary E.
Yao, Chaoqun
Extracellular release of virulence factor major surface protease via exosomes in Leishmania infantum promastigotes
title Extracellular release of virulence factor major surface protease via exosomes in Leishmania infantum promastigotes
title_full Extracellular release of virulence factor major surface protease via exosomes in Leishmania infantum promastigotes
title_fullStr Extracellular release of virulence factor major surface protease via exosomes in Leishmania infantum promastigotes
title_full_unstemmed Extracellular release of virulence factor major surface protease via exosomes in Leishmania infantum promastigotes
title_short Extracellular release of virulence factor major surface protease via exosomes in Leishmania infantum promastigotes
title_sort extracellular release of virulence factor major surface protease via exosomes in leishmania infantum promastigotes
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006689/
https://www.ncbi.nlm.nih.gov/pubmed/29921321
http://dx.doi.org/10.1186/s13071-018-2937-y
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