Cargando…

Leishmania Exosomes/Extracellular Vesicles Containing GP63 Are Essential for Enhance Cutaneous Leishmaniasis Development Upon Co-Inoculation of Leishmania amazonensis and Its Exosomes

Protozoan parasites of the genus Leishmania are transmitted by the bite of infected sand flies leading to a wide range of diseases called leishmaniasis. Recently, we demonstrated that Leishmania spp.-derived exosomes/extracellular vesicles (EVs/LeishEXO) were released in the lumen of the sand fly mi...

Descripción completa

Detalles Bibliográficos
Autores principales: da Silva Lira Filho, Alonso, Fajardo, Emanuella Francisco, Chang, Kwang Poo, Clément, Pauline, Olivier, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851419/
https://www.ncbi.nlm.nih.gov/pubmed/35186777
http://dx.doi.org/10.3389/fcimb.2021.709258
_version_ 1784652816435904512
author da Silva Lira Filho, Alonso
Fajardo, Emanuella Francisco
Chang, Kwang Poo
Clément, Pauline
Olivier, Martin
author_facet da Silva Lira Filho, Alonso
Fajardo, Emanuella Francisco
Chang, Kwang Poo
Clément, Pauline
Olivier, Martin
author_sort da Silva Lira Filho, Alonso
collection PubMed
description Protozoan parasites of the genus Leishmania are transmitted by the bite of infected sand flies leading to a wide range of diseases called leishmaniasis. Recently, we demonstrated that Leishmania spp.-derived exosomes/extracellular vesicles (EVs/LeishEXO) were released in the lumen of the sand fly midgut and to be co-egested with the parasite during the blood meal and that LeishEXO were found to stimulate an inflammatory response conducting to an exacerbated cutaneous leishmaniasis, also it was shown that these vesicles cargo important virulence factors like GP63. Thus, this study aimed to confirm through morphological and proteomic analysis a novel model specificity utilizing another set of GP63-altered Leishmania amazonensis parasite strains. Consequently, we proposed to further study the impact of different GP63 vesicle expression levels on their ability to modulate innate inflammatory cell responses, and finally to determine the importance of GP63 vesicle content on the exacerbation of the cutaneous Leishmania spp. pathology after their host co-inoculation. Our results revealed that the protein composition of extracted extracellular vesicles were similar to each other and that GP63 was the sole virulence factor changed in the exosomes composition confirming the specificity of the chosen novel model. We further demonstrated that vesicles with different GP63 EVs cargo displayed distinctive macrophage immunomodulatory capabilities at both gene and protein expression in vitro. Finally, we showed their diverse impact on the Leishmania spp. cutaneous pathology in an in vivo setting and confirmed GP63 as a primordial component of the ability of these EVs in augmenting the inflammatory cutaneous response in Leishmania spp. infection. Our findings provide new insight on the immune response happening in cutaneous leishmaniasis, shade light on the mechanism behind the host-pathogen interaction occurring in the initial moments of infection, thus creating the opportunity of using them as the target of new pharmacological treatments and vaccinations.
format Online
Article
Text
id pubmed-8851419
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-88514192022-02-18 Leishmania Exosomes/Extracellular Vesicles Containing GP63 Are Essential for Enhance Cutaneous Leishmaniasis Development Upon Co-Inoculation of Leishmania amazonensis and Its Exosomes da Silva Lira Filho, Alonso Fajardo, Emanuella Francisco Chang, Kwang Poo Clément, Pauline Olivier, Martin Front Cell Infect Microbiol Cellular and Infection Microbiology Protozoan parasites of the genus Leishmania are transmitted by the bite of infected sand flies leading to a wide range of diseases called leishmaniasis. Recently, we demonstrated that Leishmania spp.-derived exosomes/extracellular vesicles (EVs/LeishEXO) were released in the lumen of the sand fly midgut and to be co-egested with the parasite during the blood meal and that LeishEXO were found to stimulate an inflammatory response conducting to an exacerbated cutaneous leishmaniasis, also it was shown that these vesicles cargo important virulence factors like GP63. Thus, this study aimed to confirm through morphological and proteomic analysis a novel model specificity utilizing another set of GP63-altered Leishmania amazonensis parasite strains. Consequently, we proposed to further study the impact of different GP63 vesicle expression levels on their ability to modulate innate inflammatory cell responses, and finally to determine the importance of GP63 vesicle content on the exacerbation of the cutaneous Leishmania spp. pathology after their host co-inoculation. Our results revealed that the protein composition of extracted extracellular vesicles were similar to each other and that GP63 was the sole virulence factor changed in the exosomes composition confirming the specificity of the chosen novel model. We further demonstrated that vesicles with different GP63 EVs cargo displayed distinctive macrophage immunomodulatory capabilities at both gene and protein expression in vitro. Finally, we showed their diverse impact on the Leishmania spp. cutaneous pathology in an in vivo setting and confirmed GP63 as a primordial component of the ability of these EVs in augmenting the inflammatory cutaneous response in Leishmania spp. infection. Our findings provide new insight on the immune response happening in cutaneous leishmaniasis, shade light on the mechanism behind the host-pathogen interaction occurring in the initial moments of infection, thus creating the opportunity of using them as the target of new pharmacological treatments and vaccinations. Frontiers Media S.A. 2022-02-03 /pmc/articles/PMC8851419/ /pubmed/35186777 http://dx.doi.org/10.3389/fcimb.2021.709258 Text en Copyright © 2022 da Silva Lira Filho, Fajardo, Chang, Clément and Olivier 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
da Silva Lira Filho, Alonso
Fajardo, Emanuella Francisco
Chang, Kwang Poo
Clément, Pauline
Olivier, Martin
Leishmania Exosomes/Extracellular Vesicles Containing GP63 Are Essential for Enhance Cutaneous Leishmaniasis Development Upon Co-Inoculation of Leishmania amazonensis and Its Exosomes
title Leishmania Exosomes/Extracellular Vesicles Containing GP63 Are Essential for Enhance Cutaneous Leishmaniasis Development Upon Co-Inoculation of Leishmania amazonensis and Its Exosomes
title_full Leishmania Exosomes/Extracellular Vesicles Containing GP63 Are Essential for Enhance Cutaneous Leishmaniasis Development Upon Co-Inoculation of Leishmania amazonensis and Its Exosomes
title_fullStr Leishmania Exosomes/Extracellular Vesicles Containing GP63 Are Essential for Enhance Cutaneous Leishmaniasis Development Upon Co-Inoculation of Leishmania amazonensis and Its Exosomes
title_full_unstemmed Leishmania Exosomes/Extracellular Vesicles Containing GP63 Are Essential for Enhance Cutaneous Leishmaniasis Development Upon Co-Inoculation of Leishmania amazonensis and Its Exosomes
title_short Leishmania Exosomes/Extracellular Vesicles Containing GP63 Are Essential for Enhance Cutaneous Leishmaniasis Development Upon Co-Inoculation of Leishmania amazonensis and Its Exosomes
title_sort leishmania exosomes/extracellular vesicles containing gp63 are essential for enhance cutaneous leishmaniasis development upon co-inoculation of leishmania amazonensis and its exosomes
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851419/
https://www.ncbi.nlm.nih.gov/pubmed/35186777
http://dx.doi.org/10.3389/fcimb.2021.709258
work_keys_str_mv AT dasilvalirafilhoalonso leishmaniaexosomesextracellularvesiclescontaininggp63areessentialforenhancecutaneousleishmaniasisdevelopmentuponcoinoculationofleishmaniaamazonensisanditsexosomes
AT fajardoemanuellafrancisco leishmaniaexosomesextracellularvesiclescontaininggp63areessentialforenhancecutaneousleishmaniasisdevelopmentuponcoinoculationofleishmaniaamazonensisanditsexosomes
AT changkwangpoo leishmaniaexosomesextracellularvesiclescontaininggp63areessentialforenhancecutaneousleishmaniasisdevelopmentuponcoinoculationofleishmaniaamazonensisanditsexosomes
AT clementpauline leishmaniaexosomesextracellularvesiclescontaininggp63areessentialforenhancecutaneousleishmaniasisdevelopmentuponcoinoculationofleishmaniaamazonensisanditsexosomes
AT oliviermartin leishmaniaexosomesextracellularvesiclescontaininggp63areessentialforenhancecutaneousleishmaniasisdevelopmentuponcoinoculationofleishmaniaamazonensisanditsexosomes