Total free lipids from MDR strain of Mycobacterium tuberculosis “M” reduce T cell activation and CTL activity in healthy individuals
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 en...
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| Format: | info:ar-repo/semantics/artículo |
| Language: | Inglés |
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Elsevier
2025
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| Online Access: | 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 |
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| author | Bigi, María Mercedes Imperiale, Belen Rocio Soria, Marcelo Abel López, Beatriz Bigi, Fabiana Barrera, Silvia Susana de la |
| author_browse | Barrera, Silvia Susana de la Bigi, Fabiana Bigi, María Mercedes Imperiale, Belen Rocio López, Beatriz Soria, Marcelo Abel |
| author_facet | Bigi, María Mercedes Imperiale, Belen Rocio Soria, Marcelo Abel López, Beatriz Bigi, Fabiana Barrera, Silvia Susana de la |
| author_sort | Bigi, María Mercedes |
| collection | INTA Digital |
| 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. |
| format | info:ar-repo/semantics/artículo |
| id | INTA22373 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| record_format | dspace |
| spelling | INTA223732025-05-22T12:04:25Z Total free lipids from MDR strain of Mycobacterium tuberculosis “M” reduce T cell activation and CTL activity in healthy individuals Bigi, María Mercedes Imperiale, Belen Rocio Soria, Marcelo Abel López, Beatriz Bigi, Fabiana Barrera, Silvia Susana de la Mycobacterium tuberculosis Respuesta Inmunológica Lípidos Immune Response Lipids 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 2025-05-22T11:57:52Z 2025-05-22T11:57:52Z 2025-07 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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 eng 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? 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) application/pdf Elsevier Molecular Immunology 183 : 182-193 (July 2025) |
| spellingShingle | Mycobacterium tuberculosis Respuesta Inmunológica Lípidos Immune Response Lipids Bigi, María Mercedes Imperiale, Belen Rocio Soria, Marcelo Abel López, Beatriz Bigi, Fabiana Barrera, Silvia Susana de la 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 |
| 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_short | 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 |
| topic | Mycobacterium tuberculosis Respuesta Inmunológica Lípidos Immune Response Lipids |
| 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 |
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