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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Microbial Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1484143
This article is part of the Research Topic Immune Response in Tuberculosis with Comorbidities or Coinfections View all 7 articles

Specific immune response to M. tuberculosis and ability to in vitro control mycobacterial replication in patients with tuberculosis infection are not impaired in subjects with immune-mediated inflammatory disease

Provisionally accepted
Chiara Farroni Chiara Farroni 1Anna Maria Gerarda Altera Anna Maria Gerarda Altera 1Andrea Salmi Andrea Salmi 1Valentina Vanini Valentina Vanini 1,2Gilda Cuzzi Gilda Cuzzi 1Cecilia Lindestam Arlehamn Cecilia Lindestam Arlehamn 3Alessandro Sette Alessandro Sette 3Giovanni Delogu Giovanni Delogu 4,5Ivana Palucci Ivana Palucci 4SETTIMIA SBARRA SETTIMIA SBARRA 1Alessandra Aiello Alessandra Aiello 1Andrea Picchianti-Diamanti Andrea Picchianti-Diamanti 6Gina Gualano Gina Gualano 7Fabrizio Palmieri Fabrizio Palmieri 7Delia Goletti Delia Goletti 1*Elisa Petruccioli Elisa Petruccioli 1
  • 1 Translational Research Unit National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, Rome, Italy
  • 2 UOS Professioni Sanitarie Tecniche, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Lazio, Italy
  • 3 Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, California, United States
  • 4 Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy, Rome, Italy
  • 5 Mater Olbia Hospital, Olbia, Italy
  • 6 Department of Clinical and Molecular Medicine, "Sapienza" University, S. Andrea University Hospital, 00189, Rome, Lazio, Italy
  • 7 Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, 00149 Rome, Italy., Rome, Lazio, Italy

The final, formatted version of the article will be published soon.

    Background: Subjects 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. Methods: We 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. Results: The 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. Conclusion: IMID 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.

    Keywords: Tuberculosis, Rheumatoid arthritis, Th1, Antigen-specific response, AIM assay; IFN-γ, MGIA

    Received: 21 Aug 2024; Accepted: 19 Dec 2024.

    Copyright: © 2024 Farroni, Altera, Salmi, Vanini, Cuzzi, Lindestam Arlehamn, Sette, Delogu, Palucci, SBARRA, Aiello, Picchianti-Diamanti, Gualano, Palmieri, Goletti and Petruccioli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Delia Goletti, Translational Research Unit National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, Rome, Italy

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