Total free lipids from MDR strain of Mycobacterium tuberculosis “M” reduce T cell activation and CTL activity in healthy individuals

Autores
Bigi, María Mercedes; Imperiale, Belen Rocio; Soria, Marcelo Abel; López, Beatriz; Bigi, Fabiana; Barrera, Silvia Susana de la
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Increasing evidence highlights the role of cell wall components in the effectiveness of different Mycobacterium tuberculosis (Mtb) strains in modulating host immune response. We previously demonstrated that the outbreak multidrug-resistant strain M displays a distinctive lipid profile in its cell envelope compared to the closely related sporadic strain 410. Both strains markedly differ in their ability to induce fully functional CD8+ T cells because of low CD69 signaling and impaired CD4+ T cell help. In this study, we evaluated the impact of extractable lipids (LP) from M (LP-M) and 410 (LP-410) on the activation and functionality of T cells from healthy individuals. PBMCs were cultured alone or with Mtb in the presence or absence of LP-M, LP-410, or LP from CD1551 mutants in polymorphic genes between M and 410. Then, surface CD69 and intracytoplasmic IL-2 (after 3 days of culture), as well as surface CD107 expression (after 6 days of culture) were determined in T cells by flow cytometry. In contrast to LP-410, LP-M induced low expression of CD69 and IL-2 in CD4+/CD8+ cells and of CD107 in CD8+ cells. Besides, LP from Mtb strains mutated in Rv1861c and Rv3787c genes inhibited H37Rv-induced T cell response without causing cell death. Thus, our results suggest that LP-M likely through mutations in Rv1861 and Rv3787c, inhibits the activation and functionality of T cells from PPD+ healthy human donors and might partially contribute to the development of immune evasion mechanisms in the M strain.
Instituto de Biotecnología
Fil: Bigi, María Mercedes. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Bigi, María Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Imperiale, Belen Rocio. Academia Nacional de Medicina. Instituto de Medicina Experimental (IMEX); Argentina
Fil: Imperiale, Belen Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Soria, Marcelo Abel. Universidad de Buenos Aires. Facultad de Agronomía; Argentina
Fil: López, Beatriz. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas “Dr. Carlos G. Malbrán”. Laboratorio de Micobacterias; Argentina
Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Bigi, Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: de la Barrera, Silvia Susana. Academia Nacional de Medicina. Instituto de Medicina Experimental (IMEX); Argentina
Fuente
Molecular Immunology 183 : 182-193 (July 2025)
Materia
Mycobacterium tuberculosis
Respuesta Inmunológica
Lípidos
Immune Response
Lipids
Nivel de accesibilidad
acceso restringido
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/22373
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oai_identifier_str oai:localhost:20.500.12123/22373
network_acronym_str INTADig
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network_name_str INTA Digital (INTA)
spelling Total free lipids from MDR strain of Mycobacterium tuberculosis “M” reduce T cell activation and CTL activity in healthy individualsBigi, María MercedesImperiale, Belen RocioSoria, Marcelo AbelLópez, BeatrizBigi, FabianaBarrera, Silvia Susana de laMycobacterium tuberculosisRespuesta InmunológicaLípidosImmune ResponseLipidsIncreasing evidence highlights the role of cell wall components in the effectiveness of different Mycobacterium tuberculosis (Mtb) strains in modulating host immune response. We previously demonstrated that the outbreak multidrug-resistant strain M displays a distinctive lipid profile in its cell envelope compared to the closely related sporadic strain 410. Both strains markedly differ in their ability to induce fully functional CD8+ T cells because of low CD69 signaling and impaired CD4+ T cell help. In this study, we evaluated the impact of extractable lipids (LP) from M (LP-M) and 410 (LP-410) on the activation and functionality of T cells from healthy individuals. PBMCs were cultured alone or with Mtb in the presence or absence of LP-M, LP-410, or LP from CD1551 mutants in polymorphic genes between M and 410. Then, surface CD69 and intracytoplasmic IL-2 (after 3 days of culture), as well as surface CD107 expression (after 6 days of culture) were determined in T cells by flow cytometry. In contrast to LP-410, LP-M induced low expression of CD69 and IL-2 in CD4+/CD8+ cells and of CD107 in CD8+ cells. Besides, LP from Mtb strains mutated in Rv1861c and Rv3787c genes inhibited H37Rv-induced T cell response without causing cell death. Thus, our results suggest that LP-M likely through mutations in Rv1861 and Rv3787c, inhibits the activation and functionality of T cells from PPD+ healthy human donors and might partially contribute to the development of immune evasion mechanisms in the M strain.Instituto de BiotecnologíaFil: Bigi, María Mercedes. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Bigi, María Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Imperiale, Belen Rocio. Academia Nacional de Medicina. Instituto de Medicina Experimental (IMEX); ArgentinaFil: Imperiale, Belen Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Soria, Marcelo Abel. Universidad de Buenos Aires. Facultad de Agronomía; ArgentinaFil: López, Beatriz. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas “Dr. Carlos G. Malbrán”. Laboratorio de Micobacterias; ArgentinaFil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Bigi, Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de la Barrera, Silvia Susana. Academia Nacional de Medicina. Instituto de Medicina Experimental (IMEX); ArgentinaElsevier2025-05-22T11:57:52Z2025-05-22T11:57:52Z2025-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/22373https://www.sciencedirect.com/science/article/abs/pii/S01615890250012701872-9142https://doi.org/10.1016/j.molimm.2025.05.007Molecular Immunology 183 : 182-193 (July 2025)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repograntAgreement/INTA/2019-PD-E6-I116-001, Identificación y análisis funcional de genes o redes génicas de interés biotecnológico con fin agropecuario, forestal, agroalimentario y/o agroindustrialinfo:eu-repograntAgreement/INTA/2019-PD-E5-I105-001, Patógenos animales: su interacción con el hospedador y el medio ambiente. Impacto en productividad, ecosistemas, sanidad animal y salud pública en el marco ?Una Salud?info:eu-repo/semantics/restrictedAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2025-10-16T09:32:17Zoai:localhost:20.500.12123/22373instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-10-16 09:32:18.352INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Total free lipids from MDR strain of Mycobacterium tuberculosis “M” reduce T cell activation and CTL activity in healthy individuals
title Total free lipids from MDR strain of Mycobacterium tuberculosis “M” reduce T cell activation and CTL activity in healthy individuals
spellingShingle Total free lipids from MDR strain of Mycobacterium tuberculosis “M” reduce T cell activation and CTL activity in healthy individuals
Bigi, María Mercedes
Mycobacterium tuberculosis
Respuesta Inmunológica
Lípidos
Immune Response
Lipids
title_short Total free lipids from MDR strain of Mycobacterium tuberculosis “M” reduce T cell activation and CTL activity in healthy individuals
title_full Total free lipids from MDR strain of Mycobacterium tuberculosis “M” reduce T cell activation and CTL activity in healthy individuals
title_fullStr Total free lipids from MDR strain of Mycobacterium tuberculosis “M” reduce T cell activation and CTL activity in healthy individuals
title_full_unstemmed Total free lipids from MDR strain of Mycobacterium tuberculosis “M” reduce T cell activation and CTL activity in healthy individuals
title_sort Total free lipids from MDR strain of Mycobacterium tuberculosis “M” reduce T cell activation and CTL activity in healthy individuals
dc.creator.none.fl_str_mv Bigi, María Mercedes
Imperiale, Belen Rocio
Soria, Marcelo Abel
López, Beatriz
Bigi, Fabiana
Barrera, Silvia Susana de la
author Bigi, María Mercedes
author_facet Bigi, María Mercedes
Imperiale, Belen Rocio
Soria, Marcelo Abel
López, Beatriz
Bigi, Fabiana
Barrera, Silvia Susana de la
author_role author
author2 Imperiale, Belen Rocio
Soria, Marcelo Abel
López, Beatriz
Bigi, Fabiana
Barrera, Silvia Susana de la
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Mycobacterium tuberculosis
Respuesta Inmunológica
Lípidos
Immune Response
Lipids
topic Mycobacterium tuberculosis
Respuesta Inmunológica
Lípidos
Immune Response
Lipids
dc.description.none.fl_txt_mv Increasing evidence highlights the role of cell wall components in the effectiveness of different Mycobacterium tuberculosis (Mtb) strains in modulating host immune response. We previously demonstrated that the outbreak multidrug-resistant strain M displays a distinctive lipid profile in its cell envelope compared to the closely related sporadic strain 410. Both strains markedly differ in their ability to induce fully functional CD8+ T cells because of low CD69 signaling and impaired CD4+ T cell help. In this study, we evaluated the impact of extractable lipids (LP) from M (LP-M) and 410 (LP-410) on the activation and functionality of T cells from healthy individuals. PBMCs were cultured alone or with Mtb in the presence or absence of LP-M, LP-410, or LP from CD1551 mutants in polymorphic genes between M and 410. Then, surface CD69 and intracytoplasmic IL-2 (after 3 days of culture), as well as surface CD107 expression (after 6 days of culture) were determined in T cells by flow cytometry. In contrast to LP-410, LP-M induced low expression of CD69 and IL-2 in CD4+/CD8+ cells and of CD107 in CD8+ cells. Besides, LP from Mtb strains mutated in Rv1861c and Rv3787c genes inhibited H37Rv-induced T cell response without causing cell death. Thus, our results suggest that LP-M likely through mutations in Rv1861 and Rv3787c, inhibits the activation and functionality of T cells from PPD+ healthy human donors and might partially contribute to the development of immune evasion mechanisms in the M strain.
Instituto de Biotecnología
Fil: Bigi, María Mercedes. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Bigi, María Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Imperiale, Belen Rocio. Academia Nacional de Medicina. Instituto de Medicina Experimental (IMEX); Argentina
Fil: Imperiale, Belen Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Soria, Marcelo Abel. Universidad de Buenos Aires. Facultad de Agronomía; Argentina
Fil: López, Beatriz. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas “Dr. Carlos G. Malbrán”. Laboratorio de Micobacterias; Argentina
Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Bigi, Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: de la Barrera, Silvia Susana. Academia Nacional de Medicina. Instituto de Medicina Experimental (IMEX); Argentina
description Increasing evidence highlights the role of cell wall components in the effectiveness of different Mycobacterium tuberculosis (Mtb) strains in modulating host immune response. We previously demonstrated that the outbreak multidrug-resistant strain M displays a distinctive lipid profile in its cell envelope compared to the closely related sporadic strain 410. Both strains markedly differ in their ability to induce fully functional CD8+ T cells because of low CD69 signaling and impaired CD4+ T cell help. In this study, we evaluated the impact of extractable lipids (LP) from M (LP-M) and 410 (LP-410) on the activation and functionality of T cells from healthy individuals. PBMCs were cultured alone or with Mtb in the presence or absence of LP-M, LP-410, or LP from CD1551 mutants in polymorphic genes between M and 410. Then, surface CD69 and intracytoplasmic IL-2 (after 3 days of culture), as well as surface CD107 expression (after 6 days of culture) were determined in T cells by flow cytometry. In contrast to LP-410, LP-M induced low expression of CD69 and IL-2 in CD4+/CD8+ cells and of CD107 in CD8+ cells. Besides, LP from Mtb strains mutated in Rv1861c and Rv3787c genes inhibited H37Rv-induced T cell response without causing cell death. Thus, our results suggest that LP-M likely through mutations in Rv1861 and Rv3787c, inhibits the activation and functionality of T cells from PPD+ healthy human donors and might partially contribute to the development of immune evasion mechanisms in the M strain.
publishDate 2025
dc.date.none.fl_str_mv 2025-05-22T11:57:52Z
2025-05-22T11:57:52Z
2025-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12123/22373
https://www.sciencedirect.com/science/article/abs/pii/S0161589025001270
1872-9142
https://doi.org/10.1016/j.molimm.2025.05.007
url http://hdl.handle.net/20.500.12123/22373
https://www.sciencedirect.com/science/article/abs/pii/S0161589025001270
https://doi.org/10.1016/j.molimm.2025.05.007
identifier_str_mv 1872-9142
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repograntAgreement/INTA/2019-PD-E6-I116-001, Identificación y análisis funcional de genes o redes génicas de interés biotecnológico con fin agropecuario, forestal, agroalimentario y/o agroindustrial
info:eu-repograntAgreement/INTA/2019-PD-E5-I105-001, Patógenos animales: su interacción con el hospedador y el medio ambiente. Impacto en productividad, ecosistemas, sanidad animal y salud pública en el marco ?Una Salud?
dc.rights.none.fl_str_mv info:eu-repo/semantics/restrictedAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv restrictedAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Molecular Immunology 183 : 182-193 (July 2025)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
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