Immunomodulatory properties of Leishmania tarentolae extracellular vesicles containing the Spike protein of SARS-CoV-2
Extracellular vesicles released by the protozoan parasite Leishmania display immunomodulatory properties towards mammalian immune cells. In this study, we have evaluated the potential of extracellular vesicles derived from the non-pathogenic protozoan Leishmania tarentolae towards the development of...
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| Format: | Article |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Parasitology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpara.2024.1306478/full |
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| author | Ana Catalina Medina Ana Catalina Medina Hamlet Acevedo Ospina Hamlet Acevedo Ospina Albert Descoteaux Albert Descoteaux |
| author_facet | Ana Catalina Medina Ana Catalina Medina Hamlet Acevedo Ospina Hamlet Acevedo Ospina Albert Descoteaux Albert Descoteaux |
| author_sort | Ana Catalina Medina |
| collection | DOAJ |
| description | Extracellular vesicles released by the protozoan parasite Leishmania display immunomodulatory properties towards mammalian immune cells. In this study, we have evaluated the potential of extracellular vesicles derived from the non-pathogenic protozoan Leishmania tarentolae towards the development of a vaccine adjuvant. As a proof of concept, we expressed in L. tarentolae a codon-optimized SARS-CoV-2 Spike protein fused to the L. mexicana secreted acid phosphatase signal peptide in the N-terminal and to a 6×-His stretch in the C-terminal. Extracellular vesicles released by the engineered L. tarentolae were isolated by ultracentrifugation and fast protein liquid chromatography and were characterized via nanoparticle tracking analysis and transmission electron microscopy. The recombinant S protein was present in extracellular vesicles released by L. tarentolae, as determined by Western blot analyses and immunoelectron microscopy. Next, we evaluated the immunomodulatory potential of extracellular vesicles containing the S protein towards bone-marrow-derived macrophages and bone-marrow-derived dendritic cells. Our data show that in bone-marrow-derived dendritic cells, extracellular vesicles containing the S protein induced an increased expression of proinflammatory genes compared to plain extracellular vesicles whereas the opposite was observed in bone-marrow-derived macrophages. These findings reveal the immunomodulatory potential of L. tarentolae extracellular vesicles and provide a proof of concept that they can be used as adjuvant in the context of dendritic cell stimulation. |
| first_indexed | 2024-04-24T12:30:39Z |
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| id | doaj.art-65a60ebc6d854c7ab5c55967fe0a60e2 |
| institution | Directory Open Access Journal |
| issn | 2813-2424 |
| language | English |
| last_indexed | 2024-04-24T12:30:39Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Parasitology |
| spelling | doaj.art-65a60ebc6d854c7ab5c55967fe0a60e22024-04-08T04:52:42ZengFrontiers Media S.A.Frontiers in Parasitology2813-24242024-04-01310.3389/fpara.2024.13064781306478Immunomodulatory properties of Leishmania tarentolae extracellular vesicles containing the Spike protein of SARS-CoV-2Ana Catalina Medina0Ana Catalina Medina1Hamlet Acevedo Ospina2Hamlet Acevedo Ospina3Albert Descoteaux4Albert Descoteaux5INRS- Centre Armand-Frappier Santé Biotechnologie, Université du Québec, Laval, QC, CanadaInfectiopôle INRS, Laval, QC, CanadaINRS- Centre Armand-Frappier Santé Biotechnologie, Université du Québec, Laval, QC, CanadaInfectiopôle INRS, Laval, QC, CanadaINRS- Centre Armand-Frappier Santé Biotechnologie, Université du Québec, Laval, QC, CanadaInfectiopôle INRS, Laval, QC, CanadaExtracellular vesicles released by the protozoan parasite Leishmania display immunomodulatory properties towards mammalian immune cells. In this study, we have evaluated the potential of extracellular vesicles derived from the non-pathogenic protozoan Leishmania tarentolae towards the development of a vaccine adjuvant. As a proof of concept, we expressed in L. tarentolae a codon-optimized SARS-CoV-2 Spike protein fused to the L. mexicana secreted acid phosphatase signal peptide in the N-terminal and to a 6×-His stretch in the C-terminal. Extracellular vesicles released by the engineered L. tarentolae were isolated by ultracentrifugation and fast protein liquid chromatography and were characterized via nanoparticle tracking analysis and transmission electron microscopy. The recombinant S protein was present in extracellular vesicles released by L. tarentolae, as determined by Western blot analyses and immunoelectron microscopy. Next, we evaluated the immunomodulatory potential of extracellular vesicles containing the S protein towards bone-marrow-derived macrophages and bone-marrow-derived dendritic cells. Our data show that in bone-marrow-derived dendritic cells, extracellular vesicles containing the S protein induced an increased expression of proinflammatory genes compared to plain extracellular vesicles whereas the opposite was observed in bone-marrow-derived macrophages. These findings reveal the immunomodulatory potential of L. tarentolae extracellular vesicles and provide a proof of concept that they can be used as adjuvant in the context of dendritic cell stimulation.https://www.frontiersin.org/articles/10.3389/fpara.2024.1306478/fullLeishmaniaSpike proteinSARS-CoV2extracellular vesiclesdendritic cellsmacrophages |
| spellingShingle | Ana Catalina Medina Ana Catalina Medina Hamlet Acevedo Ospina Hamlet Acevedo Ospina Albert Descoteaux Albert Descoteaux Immunomodulatory properties of Leishmania tarentolae extracellular vesicles containing the Spike protein of SARS-CoV-2 Frontiers in Parasitology Leishmania Spike protein SARS-CoV2 extracellular vesicles dendritic cells macrophages |
| title | Immunomodulatory properties of Leishmania tarentolae extracellular vesicles containing the Spike protein of SARS-CoV-2 |
| title_full | Immunomodulatory properties of Leishmania tarentolae extracellular vesicles containing the Spike protein of SARS-CoV-2 |
| title_fullStr | Immunomodulatory properties of Leishmania tarentolae extracellular vesicles containing the Spike protein of SARS-CoV-2 |
| title_full_unstemmed | Immunomodulatory properties of Leishmania tarentolae extracellular vesicles containing the Spike protein of SARS-CoV-2 |
| title_short | Immunomodulatory properties of Leishmania tarentolae extracellular vesicles containing the Spike protein of SARS-CoV-2 |
| title_sort | immunomodulatory properties of leishmania tarentolae extracellular vesicles containing the spike protein of sars cov 2 |
| topic | Leishmania Spike protein SARS-CoV2 extracellular vesicles dendritic cells macrophages |
| url | https://www.frontiersin.org/articles/10.3389/fpara.2024.1306478/full |
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