Specific immune response to M. tuberculosis and ability to in vitro control mycobacterial replication are not impaired in subjects with immune-mediated inflammatory disease and tuberculosis infection
BackgroundSubjects with immune-mediated inflammatory diseases (IMID), such as rheumatoid arthritis, with tuberculosis infection (TBI), have a high probability of progressing to tuberculosis disease (TB). We aim to characterize the impact of IMID on the immune response to M. tuberculosis (Mtb) in pat...
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Frontiers Media S.A.
2025-01-01
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| author | Chiara Farroni Anna Maria Gerarda Altera Andrea Salmi Valentina Vanini Valentina Vanini Gilda Cuzzi Cecilia S. Lindestam Arlehamn Alessandro Sette Giovanni Delogu Giovanni Delogu Ivana Palucci Settimia Sbarra Alessandra Aiello Andrea Picchianti-Diamanti Gina Gualano Fabrizio Palmieri Delia Goletti Elisa Petruccioli |
| author_facet | Chiara Farroni Anna Maria Gerarda Altera Andrea Salmi Valentina Vanini Valentina Vanini Gilda Cuzzi Cecilia S. Lindestam Arlehamn Alessandro Sette Giovanni Delogu Giovanni Delogu Ivana Palucci Settimia Sbarra Alessandra Aiello Andrea Picchianti-Diamanti Gina Gualano Fabrizio Palmieri Delia Goletti Elisa Petruccioli |
| author_sort | Chiara Farroni |
| collection | DOAJ |
| description | BackgroundSubjects with immune-mediated inflammatory diseases (IMID), such as rheumatoid arthritis, with tuberculosis infection (TBI), have a high probability of progressing to tuberculosis disease (TB). We aim to characterize the impact of IMID on the immune response to M. tuberculosis (Mtb) in patients with TBI and TB disease.MethodsWe enrolled TBI and TB patients with and without IMID. Peripheral blood mononuclear cells (PBMCs) were stimulated with Mtb-derived epitopes (MTB300). By flow-cytometry, we identified the Mtb-specific CD4+ T cells as cytokine-producing T cells or as CD25+ CD134+ CD4+ T cells. Memory and activation status of Mtb-specific T cells were assessed by evaluating: CD153, HLA-DR, CD45RA, CD27. Mycobacterial growth inhibition assay (MGIA) was used to evaluate the ability of PBMCs to inhibit mycobacteria growth. A long-term stimulation assay was used to detect a memory response.ResultsThe IMID status and therapy did not affect the magnitude of response to Mtb-antigen stimulation and the number of responders. TBI-IMID showed a cytokine profile like TBI and TB patients. The Mtb response of TBI-IMID patients was characterized by an effector memory and central memory phenotype as in TBI and TB groups. This memory phenotype allowed the increased IFN-γ production after 6 days of MTB300-stimulation. HLA-DR expression on Mtb-specific T cells was associated with TB, whereas CD153 was associated with TBI status. Finally, the TBI-IMID had an MGIA response like TBI and TB patients.ConclusionIMID condition does not affect key aspects of the immune response to Mtb, such as the cytokine response, memory and activation profile, and the ability to contain the mycobacteria replication. The immunological characterization of the fragile population of TBI-IMID patients is fundamental to understanding the correlation between protection and disease. |
| format | Article |
| id | doaj-art-fe168d574e2041d59d908f85dc2da4e2 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-fe168d574e2041d59d908f85dc2da4e22025-01-13T06:10:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14841431484143Specific immune response to M. tuberculosis and ability to in vitro control mycobacterial replication are not impaired in subjects with immune-mediated inflammatory disease and tuberculosis infectionChiara Farroni0Anna Maria Gerarda Altera1Andrea Salmi2Valentina Vanini3Valentina Vanini4Gilda Cuzzi5Cecilia S. Lindestam Arlehamn6Alessandro Sette7Giovanni Delogu8Giovanni Delogu9Ivana Palucci10Settimia Sbarra11Alessandra Aiello12Andrea Picchianti-Diamanti13Gina Gualano14Fabrizio Palmieri15Delia Goletti16Elisa Petruccioli17Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, ItalyTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, ItalyTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, ItalyTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, ItalyUnità Operativa Semplice (UOS) Professioni Sanitarie Tecniche, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, ItalyTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, ItalyCenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, United StatesCenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, United StatesDipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, ItalyDiagnostic Labororatory Unit, Mater Olbia Hospital, Olbia, ItalyDipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, ItalyTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, ItalyTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, ItalyDepartment of Clinical and Molecular Medicine, “Sapienza” University, S. Andrea University Hospital, Rome, ItalyRespiratory Infectious Diseases Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, ItalyRespiratory Infectious Diseases Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, ItalyTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, ItalyTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, ItalyBackgroundSubjects with immune-mediated inflammatory diseases (IMID), such as rheumatoid arthritis, with tuberculosis infection (TBI), have a high probability of progressing to tuberculosis disease (TB). We aim to characterize the impact of IMID on the immune response to M. tuberculosis (Mtb) in patients with TBI and TB disease.MethodsWe enrolled TBI and TB patients with and without IMID. Peripheral blood mononuclear cells (PBMCs) were stimulated with Mtb-derived epitopes (MTB300). By flow-cytometry, we identified the Mtb-specific CD4+ T cells as cytokine-producing T cells or as CD25+ CD134+ CD4+ T cells. Memory and activation status of Mtb-specific T cells were assessed by evaluating: CD153, HLA-DR, CD45RA, CD27. Mycobacterial growth inhibition assay (MGIA) was used to evaluate the ability of PBMCs to inhibit mycobacteria growth. A long-term stimulation assay was used to detect a memory response.ResultsThe IMID status and therapy did not affect the magnitude of response to Mtb-antigen stimulation and the number of responders. TBI-IMID showed a cytokine profile like TBI and TB patients. The Mtb response of TBI-IMID patients was characterized by an effector memory and central memory phenotype as in TBI and TB groups. This memory phenotype allowed the increased IFN-γ production after 6 days of MTB300-stimulation. HLA-DR expression on Mtb-specific T cells was associated with TB, whereas CD153 was associated with TBI status. Finally, the TBI-IMID had an MGIA response like TBI and TB patients.ConclusionIMID condition does not affect key aspects of the immune response to Mtb, such as the cytokine response, memory and activation profile, and the ability to contain the mycobacteria replication. The immunological characterization of the fragile population of TBI-IMID patients is fundamental to understanding the correlation between protection and disease.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1484143/fulltuberculosisrheumatoid arthritisTh1antigen-specific responseAIM assay, IFN-γMGIA |
| spellingShingle | Chiara Farroni Anna Maria Gerarda Altera Andrea Salmi Valentina Vanini Valentina Vanini Gilda Cuzzi Cecilia S. Lindestam Arlehamn Alessandro Sette Giovanni Delogu Giovanni Delogu Ivana Palucci Settimia Sbarra Alessandra Aiello Andrea Picchianti-Diamanti Gina Gualano Fabrizio Palmieri Delia Goletti Elisa Petruccioli Specific immune response to M. tuberculosis and ability to in vitro control mycobacterial replication are not impaired in subjects with immune-mediated inflammatory disease and tuberculosis infection Frontiers in Immunology tuberculosis rheumatoid arthritis Th1 antigen-specific response AIM assay, IFN-γ MGIA |
| title | Specific immune response to M. tuberculosis and ability to in vitro control mycobacterial replication are not impaired in subjects with immune-mediated inflammatory disease and tuberculosis infection |
| title_full | Specific immune response to M. tuberculosis and ability to in vitro control mycobacterial replication are not impaired in subjects with immune-mediated inflammatory disease and tuberculosis infection |
| title_fullStr | Specific immune response to M. tuberculosis and ability to in vitro control mycobacterial replication are not impaired in subjects with immune-mediated inflammatory disease and tuberculosis infection |
| title_full_unstemmed | Specific immune response to M. tuberculosis and ability to in vitro control mycobacterial replication are not impaired in subjects with immune-mediated inflammatory disease and tuberculosis infection |
| title_short | Specific immune response to M. tuberculosis and ability to in vitro control mycobacterial replication are not impaired in subjects with immune-mediated inflammatory disease and tuberculosis infection |
| title_sort | specific immune response to m tuberculosis and ability to in vitro control mycobacterial replication are not impaired in subjects with immune mediated inflammatory disease and tuberculosis infection |
| topic | tuberculosis rheumatoid arthritis Th1 antigen-specific response AIM assay, IFN-γ MGIA |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1484143/full |
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