Leishmania mexicana: Novel Insights of Immune Modulation through Amastigote Exosomes

Autor:	María Magdalena Aguirre-García, Rocely Buenaventura Cervantes-Sarabia, Adriana Méndez-Bernal, José Delgado-Domínguez, Alma Reyna Escalona-Montaño, Mariana Diupotex, Laura Enedina Soto-Serna, Jaime Zamora-Chimal, Ingeborg Becker, Adriana Ruiz-Remigio
Rok vydání:	2020
Předmět:	Article Subject Endosome 030231 tropical medicine Immunology chemical and pharmacologic phenomena Leishmania mexicana 03 medical and health sciences 0302 clinical medicine Immune system Immunology and Allergy Amastigote 030304 developmental biology CD86 0303 health sciences biology Chemistry Intracellular parasite General Medicine RC581-607 biology.organism_classification Microvesicles Cell biology CD1D biology.protein Immunologic diseases. Allergy Research Article
Zdroj:	Journal of Immunology Research Journal of Immunology Research, Vol 2020 (2020)
ISSN:	2314-7156 2314-8861
DOI:	10.1155/2020/8894549
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::19601029f450ca7d9fe520b45f2b437b https://doi.org/10.1155/2020/8894549 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.