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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Microbial Immunology
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1465448
Longitudinal mitochondrial bioenergetic signatures of blood monocytes and lymphocytes improve during treatment of drug-susceptible pulmonary tuberculosis patients Monocyte/lymphocyte bioenergetic signatures post-TB treatment
Provisionally accepted- 1 Africa Health Research Institute (AHRI), Durban, South Africa
- 2 Vanderbilt Tuberculosis Center, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- 3 Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- 4 Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER), Salvador, Bahia, Brazil
- 5 Laboratório de Pesquisa Clínica e Translacional, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz,, Salvador, Bahia, Brazil
- 6 Department of Infectious Diseases, University of KwaZulu-Natal, Durban, South Africa
- 7 Global Division, The Aurum Institute, Johannesburg, South Africa
- 8 University of Alabama at Birmingham, Birmingham, United States
The impact of human pulmonary tuberculosis (TB) on the bioenergetic metabolism of circulating immune cells remains elusive, as does the resolution of these effects with TB treatment. In this study, the rates of oxidative phosphorylation (OXPHOS) and glycolysis in circulating lymphocytes and monocytes of patients with drug-susceptible TB at diagnosis, 2 months, and 6 months during treatment, and at 12 months following diagnosis were investigated using extracellular flux analysis. At diagnosis, the bioenergetic parameters of both blood lymphocytes and monocytes of TB patients were severely impaired in comparison to non-TB, non-HIV infected controls. However, most bioenergetic parameters were not affected by HIV status nor glycaemic index. Treatment of TB patients restored the % spare respiratory capacity (%SRC) of the circulating lymphocytes to that observed in non-TB and non-HIV infected controls by 12 months. Treatment also improved the maximal respiration of the circulating lymphocytes and the %SRC of the circulating monocytes of the TB patients. Notably, differential correlation of the clinical and bioenergetic parameters of the monocytes and lymphocytes from the controls and TB patients at baseline and month 12 were consistent with improved metabolic health and resolution of inflammation following successful TB treatment. Network analysis of the bioenergetic parameters of the circulating immune cells with the serum cytokine levels indicated a highly co-ordinated immune response at month 6. These findings underscore the importance of metabolic health in combating TB, supporting the need for further investigation of the bioenergetic immunometabolism associated with TB infection for novel therapeutic approaches aimed at bolstering cellular energetics to enhance immune responses and expedite recovery in TB patients.
Keywords: Tuberculosis, Bioenergetic metabolism, Lymphocytes, Monocytes, TB treatment, Cytokines, SeaHorse XF96
Received: 16 Jul 2024; Accepted: 17 Oct 2024.
Copyright: © 2024 Cumming, Addicott, Maruri, Pillay, Asmal, Moodley, Barreto-Durate, Araújo-Pereira, Mazibuko, Mhlane, Mbatha, Khan, Makhari, Karim, Peetluk, Pym, Moosa, Van Der Heijden, Sterling, Andrade, Leslie and Steyn. 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:
Adrie J. Steyn, University of Alabama at Birmingham, Birmingham, United States
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