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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
Cumming, Bridgette M. et al. | Date Issued: 2024
Author
Cumming, Bridgette M.
Addicott, Kelvin W.
Maruri, Fernanda
Pillay, Vanessa
Asmal, Rukaya
Moodley, Sashen
Durate, Beatriz Barreto
Pereira, Mariana Araújo
Mazibuko, Matilda
Mhlane, Zoey
Mbatha, Nikiwe
Khan, Khadija
Makhari, Senamile
Karim, Farina
Peetluk, Lauren
Pym, Alexander S.
Moosa, Mahomed Yunus S.
Heijden, Yuri F. van der
Sterling, Timothy S.
Andrade, Bruno B.
Leslie, Alasdair
Steyn, Adrie J. C.
Affilliation
Africa Health Research Institute. University of KwaZulu-Natal. Durban, South Africa.
Africa Health Research Institute. University of KwaZulu-Natal. Durban, South Africa.
Africa Health Research Institute. University of KwaZulu-Natal. Durban, South Africa / Vanderbilt Tuberculosis Center. Vanderbilt University School of Medicine. Nashville, TN, United States.
Africa Health Research Institute. University of KwaZulu-Natal. Durban, South Africa.
Africa Health Research Institute. University of KwaZulu-Natal. Durban, South Africa.
Africa Health Research Institute. University of KwaZulu-Natal. Durban, South Africa.
Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisa Clínica e Translacional. Salvador, BA, Brasil.
Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisa Clínica e Translacional. Salvador, BA, Brasil.
Africa Health Research Institute. University of KwaZulu-Natal. Durban, South Africa.
Africa Health Research Institute. University of KwaZulu-Natal. Durban, South Africa.
Africa Health Research Institute. University of KwaZulu-Natal. Durban, South Africa.
Africa Health Research Institute. University of KwaZulu-Natal. Durban, South Africa.
Africa Health Research Institute. University of KwaZulu-Natal. Durban, South Africa.
Africa Health Research Institute. University of KwaZulu-Natal. Durban, South Africa.
Vanderbilt Tuberculosis Center. Vanderbilt University School of Medicine. Nashville, TN, United States.
Africa Health Research Institute. University of KwaZulu-Natal. Durban, South Africa.
Department of Infectious Diseases. University of KwaZulu-Natal. Durban, South Africa.
Vanderbilt Tuberculosis Center. Vanderbilt University School of Medicine. Nashville, TN, United States / Division of Infectious Diseases. Department of Medicine. Vanderbilt University School of Medicine. Nashville, TN, United States / Global Division. The Aurum Institute. Johannesburg, South Africa.
Vanderbilt Tuberculosis Center. Vanderbilt University School of Medicine. Nashville, TN, United States / Division of Infectious Diseases. Department of Medicine. Vanderbilt University School of Medicine. Nashville, TN, United States.
Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Pesquisa Clínica e Translacional. Salvador, BA, Brasil.
Africa Health Research Institute. University of KwaZulu-Natal. Durban, South Africa / Department of Infectious Diseases. University of KwaZulu-Natal. Durban, South Africa / Department of Infection and Immunity. University College of London. London, United Kingdom.
Africa Health Research Institute. University of KwaZulu-Natal. Durban, South Africa / Department of Microbiology. University of Alabama at Birmingham. Birmingham, AL, United States / Centers for AIDS Research and Free Radical Biology. University of Alabama at Birmingham. Birmingham, AL, United States.
Abstract
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 12 months after 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 and non-HIV-infected controls. However, most bioenergetic parameters were not affected by HIV status or glycemic 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 circulating lymphocytes and the %SRC of circulating monocytes of the TB patients. Notably, the differential correlation of the clinical and bioenergetic parameters of the monocytes and lymphocytes from the controls and TB patients at baseline and month 12 was consistent with improved metabolic health and resolution of inflammation following successful TB treatment. Network analysis of the bioenergetic parameters of circulating immune cells with serum cytokine levels indicated a highly coordinated 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
 
DeCS
Tuberculose
Metabolismo
Linfócitos
Monócitos
Citocinas
 
Publisher
Frontiers Media
Citation
CUMMING, Bridgette M. et al. 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. Frontiers in Immunology, v. 15, p. 1-14, 2024.
DOI
10.3389/fimmu.2024.1465448
ISSN
1664-3224