Leishmania mexicana: Novel Insights of Immune Modulation through Amastigote Exosomes
Exosomes are extracellular microvesicles of endosomal origin (multivesicular bodies, MVBs) constitutively released by eukaryotic cells by fusion of MVBs to the plasma membrane. The exosomes from Leishmania parasites contain an array of parasite molecules such as virulence factors and survival messen...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2020/8894549 |
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| author | Laura Enedina Soto-Serna Mariana Diupotex Jaime Zamora-Chimal Adriana Ruiz-Remigio José Delgado-Domínguez Rocely Buenaventura Cervantes-Sarabia Adriana Méndez-Bernal Alma Reyna Escalona-Montaño María Magdalena Aguirre-García Ingeborg Becker |
| author_facet | Laura Enedina Soto-Serna Mariana Diupotex Jaime Zamora-Chimal Adriana Ruiz-Remigio José Delgado-Domínguez Rocely Buenaventura Cervantes-Sarabia Adriana Méndez-Bernal Alma Reyna Escalona-Montaño María Magdalena Aguirre-García Ingeborg Becker |
| author_sort | Laura Enedina Soto-Serna |
| collection | DOAJ |
| description | Exosomes are extracellular microvesicles of endosomal origin (multivesicular bodies, MVBs) constitutively released by eukaryotic cells by fusion of MVBs to the plasma membrane. The exosomes from Leishmania parasites contain an array of parasite molecules such as virulence factors and survival messengers, capable of modulating the host immune response and thereby favoring the infection of the host. We here show that exosomes of L. mexicana amastigotes (aExo) contain the virulence proteins gp63 and PP2C. The incubation of aExo with bone marrow-derived macrophages (BMMs) infected with L. mexicana led to their internalization and were found to colocalize with the cellular tetraspanin CD63. Furthermore, aExo inhibited nitric oxide production of infected BMMs, permitting enhanced intracellular parasite survival. Expressions of antigen-presenting (major histocompatibility complex class I, MHC-I, and CD1d) and costimulatory (CD86 and PD-L1) molecules were modulated in a dose-dependent fashion. Whereas MHC-I, CD86 and PD-L1 expressions were diminished by exosomes, CD1d was enhanced. We conclude that aExo of L. mexicana are capable of decreasing microbicidal mechanisms of infected macrophages by inhibiting nitric oxide production, thereby enabling parasite survival. They also hamper the cellular immune response by diminishing MHC-I and CD86 on an important antigen-presenting cell, which potentially interferes with CD8 T cell activation. The enhanced CD1d expression in combination with reduction of PD-L1 on BMMs point to a potential shift of the activation route towards lipid presentations, yet the effectivity of this immune activation is not evident, since in the absence of costimulatory molecules, cellular anergy and tolerance would be expected. |
| format | Article |
| id | doaj-art-4b0a1947eea94829bb05e7fa7a083c06 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-4b0a1947eea94829bb05e7fa7a083c062025-02-03T01:27:56ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/88945498894549Leishmania mexicana: Novel Insights of Immune Modulation through Amastigote ExosomesLaura Enedina Soto-Serna0Mariana Diupotex1Jaime Zamora-Chimal2Adriana Ruiz-Remigio3José Delgado-Domínguez4Rocely Buenaventura Cervantes-Sarabia5Adriana Méndez-Bernal6Alma Reyna Escalona-Montaño7María Magdalena Aguirre-García8Ingeborg Becker9Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Hospital General de México, Dr. Balmis 148, Col. Doctores, CP 06726 Ciudad de México, MexicoUnidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Hospital General de México, Dr. Balmis 148, Col. Doctores, CP 06726 Ciudad de México, MexicoUnidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Hospital General de México, Dr. Balmis 148, Col. Doctores, CP 06726 Ciudad de México, MexicoUnidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Hospital General de México, Dr. Balmis 148, Col. Doctores, CP 06726 Ciudad de México, MexicoUnidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Hospital General de México, Dr. Balmis 148, Col. Doctores, CP 06726 Ciudad de México, MexicoUnidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Hospital General de México, Dr. Balmis 148, Col. Doctores, CP 06726 Ciudad de México, MexicoFacultad de Medicina Veterinaria y Zootecnia, Departamento de Patología y Microscopía electrónica, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Av. Universidad 3000, CP 04510 Ciudad de México, MexicoFacultad de Medicina, División de Investigación, Unidad de Investigación UNAM-INC (Instituto Nacional de Cardiología Ignacio Chávez), Juan Badiano No. 1, Col. Sección XVI, 14080 Ciudad de México, MexicoFacultad de Medicina, División de Investigación, Unidad de Investigación UNAM-INC (Instituto Nacional de Cardiología Ignacio Chávez), Juan Badiano No. 1, Col. Sección XVI, 14080 Ciudad de México, MexicoUnidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Hospital General de México, Dr. Balmis 148, Col. Doctores, CP 06726 Ciudad de México, MexicoExosomes are extracellular microvesicles of endosomal origin (multivesicular bodies, MVBs) constitutively released by eukaryotic cells by fusion of MVBs to the plasma membrane. The exosomes from Leishmania parasites contain an array of parasite molecules such as virulence factors and survival messengers, capable of modulating the host immune response and thereby favoring the infection of the host. We here show that exosomes of L. mexicana amastigotes (aExo) contain the virulence proteins gp63 and PP2C. The incubation of aExo with bone marrow-derived macrophages (BMMs) infected with L. mexicana led to their internalization and were found to colocalize with the cellular tetraspanin CD63. Furthermore, aExo inhibited nitric oxide production of infected BMMs, permitting enhanced intracellular parasite survival. Expressions of antigen-presenting (major histocompatibility complex class I, MHC-I, and CD1d) and costimulatory (CD86 and PD-L1) molecules were modulated in a dose-dependent fashion. Whereas MHC-I, CD86 and PD-L1 expressions were diminished by exosomes, CD1d was enhanced. We conclude that aExo of L. mexicana are capable of decreasing microbicidal mechanisms of infected macrophages by inhibiting nitric oxide production, thereby enabling parasite survival. They also hamper the cellular immune response by diminishing MHC-I and CD86 on an important antigen-presenting cell, which potentially interferes with CD8 T cell activation. The enhanced CD1d expression in combination with reduction of PD-L1 on BMMs point to a potential shift of the activation route towards lipid presentations, yet the effectivity of this immune activation is not evident, since in the absence of costimulatory molecules, cellular anergy and tolerance would be expected.http://dx.doi.org/10.1155/2020/8894549 |
| spellingShingle | Laura Enedina Soto-Serna Mariana Diupotex Jaime Zamora-Chimal Adriana Ruiz-Remigio José Delgado-Domínguez Rocely Buenaventura Cervantes-Sarabia Adriana Méndez-Bernal Alma Reyna Escalona-Montaño María Magdalena Aguirre-García Ingeborg Becker Leishmania mexicana: Novel Insights of Immune Modulation through Amastigote Exosomes Journal of Immunology Research |
| title | Leishmania mexicana: Novel Insights of Immune Modulation through Amastigote Exosomes |
| title_full | Leishmania mexicana: Novel Insights of Immune Modulation through Amastigote Exosomes |
| title_fullStr | Leishmania mexicana: Novel Insights of Immune Modulation through Amastigote Exosomes |
| title_full_unstemmed | Leishmania mexicana: Novel Insights of Immune Modulation through Amastigote Exosomes |
| title_short | Leishmania mexicana: Novel Insights of Immune Modulation through Amastigote Exosomes |
| title_sort | leishmania mexicana novel insights of immune modulation through amastigote exosomes |
| url | http://dx.doi.org/10.1155/2020/8894549 |
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