Longitudinal mitochondrial bioenergetic signatures of blood monocytes and lymphocytes improve during treatment of drug-susceptible pulmonary tuberculosis patients
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 monocyte...
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2024-11-01
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| author | Bridgette M. Cumming Kelvin W. Addicott Fernanda Maruri Fernanda Maruri Vanessa Pillay Rukaya Asmal Sashen Moodley Beatriz Barreto-Durate Beatriz Barreto-Durate Mariana Araújo-Pereira Mariana Araújo-Pereira Matilda Mazibuko Zoey Mhlane Nikiwe Mbatha Khadija Khan Senamile Makhari Farina Karim Lauren Peetluk Alexander S. Pym Mahomed Yunus S. Moosa Yuri F. van der Heijden Yuri F. van der Heijden Yuri F. van der Heijden Timothy S. Sterling Timothy S. Sterling Bruno B. Andrade Bruno B. Andrade Alasdair Leslie Alasdair Leslie Alasdair Leslie Adrie J. C. Steyn Adrie J. C. Steyn Adrie J. C. Steyn |
| author_facet | Bridgette M. Cumming Kelvin W. Addicott Fernanda Maruri Fernanda Maruri Vanessa Pillay Rukaya Asmal Sashen Moodley Beatriz Barreto-Durate Beatriz Barreto-Durate Mariana Araújo-Pereira Mariana Araújo-Pereira Matilda Mazibuko Zoey Mhlane Nikiwe Mbatha Khadija Khan Senamile Makhari Farina Karim Lauren Peetluk Alexander S. Pym Mahomed Yunus S. Moosa Yuri F. van der Heijden Yuri F. van der Heijden Yuri F. van der Heijden Timothy S. Sterling Timothy S. Sterling Bruno B. Andrade Bruno B. Andrade Alasdair Leslie Alasdair Leslie Alasdair Leslie Adrie J. C. Steyn Adrie J. C. Steyn Adrie J. C. Steyn |
| author_sort | Bridgette M. Cumming |
| collection | DOAJ |
| description | 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. |
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| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-11-01 |
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| series | Frontiers in Immunology |
| spelling | doaj-art-0f78e27f5bdc4e1d914413ad4f2e60ab2025-01-30T08:49:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-11-011510.3389/fimmu.2024.14654481465448Longitudinal mitochondrial bioenergetic signatures of blood monocytes and lymphocytes improve during treatment of drug-susceptible pulmonary tuberculosis patientsBridgette M. Cumming0Kelvin W. Addicott1Fernanda Maruri2Fernanda Maruri3Vanessa Pillay4Rukaya Asmal5Sashen Moodley6Beatriz Barreto-Durate7Beatriz Barreto-Durate8Mariana Araújo-Pereira9Mariana Araújo-Pereira10Matilda Mazibuko11Zoey Mhlane12Nikiwe Mbatha13Khadija Khan14Senamile Makhari15Farina Karim16Lauren Peetluk17Alexander S. Pym18Mahomed Yunus S. Moosa19Yuri F. van der Heijden20Yuri F. van der Heijden21Yuri F. van der Heijden22Timothy S. Sterling23Timothy S. Sterling24Bruno B. Andrade25Bruno B. Andrade26Alasdair Leslie27Alasdair Leslie28Alasdair Leslie29Adrie J. C. Steyn30Adrie J. C. Steyn31Adrie J. C. Steyn32Africa Health Research Institute, University of KwaZulu-Natal, Durban, South AfricaAfrica Health Research Institute, University of KwaZulu-Natal, Durban, South AfricaVanderbilt Tuberculosis Center, Vanderbilt University School of Medicine, Nashville, TN, United StatesDivision of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United StatesAfrica Health Research Institute, University of KwaZulu-Natal, Durban, South AfricaAfrica Health Research Institute, University of KwaZulu-Natal, Durban, South AfricaAfrica Health Research Institute, University of KwaZulu-Natal, Durban, South AfricaMultinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, BrazilLaboratório de Pesquisa Clínica e Translacional, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, BrazilMultinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, BrazilLaboratório de Pesquisa Clínica e Translacional, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, BrazilAfrica Health Research Institute, University of KwaZulu-Natal, Durban, South AfricaAfrica Health Research Institute, University of KwaZulu-Natal, Durban, South AfricaAfrica Health Research Institute, University of KwaZulu-Natal, Durban, South AfricaAfrica Health Research Institute, University of KwaZulu-Natal, Durban, South AfricaAfrica Health Research Institute, University of KwaZulu-Natal, Durban, South AfricaAfrica Health Research Institute, University of KwaZulu-Natal, Durban, South AfricaVanderbilt Tuberculosis Center, Vanderbilt University School of Medicine, Nashville, TN, United StatesAfrica Health Research Institute, University of KwaZulu-Natal, Durban, South AfricaDepartment of Infectious Diseases, University of KwaZulu-Natal, Durban, South AfricaVanderbilt Tuberculosis Center, Vanderbilt University School of Medicine, Nashville, TN, United StatesDivision of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United StatesGlobal Division, The Aurum Institute, Johannesburg, South AfricaVanderbilt Tuberculosis Center, Vanderbilt University School of Medicine, Nashville, TN, United StatesDivision of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United StatesMultinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, BrazilLaboratório de Pesquisa Clínica e Translacional, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, BrazilAfrica Health Research Institute, University of KwaZulu-Natal, Durban, South AfricaDepartment of Infectious Diseases, University of KwaZulu-Natal, Durban, South AfricaDepartment of Infection and Immunity, University College of London, London, United KingdomAfrica Health Research Institute, University of KwaZulu-Natal, Durban, South AfricaDepartment of Microbiology, University of Alabama at Birmingham, Birmingham, AL, United States0Centers for AIDS Research and Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, United StatesThe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1465448/fulltuberculosisbioenergetic metabolismlymphocytesmonocytesTB treatmentcytokines |
| spellingShingle | Bridgette M. Cumming Kelvin W. Addicott Fernanda Maruri Fernanda Maruri Vanessa Pillay Rukaya Asmal Sashen Moodley Beatriz Barreto-Durate Beatriz Barreto-Durate Mariana Araújo-Pereira Mariana Araújo-Pereira Matilda Mazibuko Zoey Mhlane Nikiwe Mbatha Khadija Khan Senamile Makhari Farina Karim Lauren Peetluk Alexander S. Pym Mahomed Yunus S. Moosa Yuri F. van der Heijden Yuri F. van der Heijden Yuri F. van der Heijden Timothy S. Sterling Timothy S. Sterling Bruno B. Andrade Bruno B. Andrade Alasdair Leslie Alasdair Leslie Alasdair Leslie Adrie J. C. Steyn Adrie J. C. Steyn Adrie J. C. Steyn Longitudinal mitochondrial bioenergetic signatures of blood monocytes and lymphocytes improve during treatment of drug-susceptible pulmonary tuberculosis patients Frontiers in Immunology tuberculosis bioenergetic metabolism lymphocytes monocytes TB treatment cytokines |
| title | Longitudinal mitochondrial bioenergetic signatures of blood monocytes and lymphocytes improve during treatment of drug-susceptible pulmonary tuberculosis patients |
| title_full | Longitudinal mitochondrial bioenergetic signatures of blood monocytes and lymphocytes improve during treatment of drug-susceptible pulmonary tuberculosis patients |
| title_fullStr | Longitudinal mitochondrial bioenergetic signatures of blood monocytes and lymphocytes improve during treatment of drug-susceptible pulmonary tuberculosis patients |
| title_full_unstemmed | Longitudinal mitochondrial bioenergetic signatures of blood monocytes and lymphocytes improve during treatment of drug-susceptible pulmonary tuberculosis patients |
| title_short | Longitudinal mitochondrial bioenergetic signatures of blood monocytes and lymphocytes improve during treatment of drug-susceptible pulmonary tuberculosis patients |
| title_sort | longitudinal mitochondrial bioenergetic signatures of blood monocytes and lymphocytes improve during treatment of drug susceptible pulmonary tuberculosis patients |
| topic | tuberculosis bioenergetic metabolism lymphocytes monocytes TB treatment cytokines |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1465448/full |
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