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
- Institución
- Instituto Nacional de Tecnología Agropecuaria
- OAI Identificador
- oai:localhost:20.500.12123/22373
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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)2025-09-29T13:47:18Zoai: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:l2025-09-29 13:47:18.823INTA 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 |
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INTA Digital (INTA) |
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INTA Digital (INTA) |
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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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