Effect of TB Treatment on Neutrophil-Derived Soluble Inflammatory Mediators in TB Patients with and without HIV Coinfection

The mycobacteriological analysis of sputum samples is the gold standard for tuberculosis diagnosis and treatment monitoring. However, sputum production can be challenging after the initiation of TB treatment. As a possible alternative, we therefore investigated the dynamics of neutrophil-derived soluble inflammatory mediators during TB treatment in relation to HIV ART status and the severity of lung impairment. Plasma samples of TB patients with (N = 47) and without HIV (N = 21) were analyzed at baseline, month 2, month 6 (end of TB treatment) and month 12. Plasma levels of MMP-1, MMP-8, MPO and S100A8 markedly decreased over the course of TB treatment and remained at similar levels thereafter. Post-TB treatment initiation, significantly elevated plasma levels of MMP-8 were detected in TB patients living with HIV, especially if they were not receiving ART treatment at baseline. Our data confirm that the plasma levels of neutrophil-based biomarkers can be used as candidate surrogate markers for TB treatment outcome and HIV-infection influenced MMP-8 and S100A8 levels. Future studies to validate our results and to understand the dynamics of neutrophils-based biomarkers post-TB treatment are needed.

[1]  A. Martineau,et al.  Inflammation-mediated tissue damage in pulmonary tuberculosis and host-directed therapeutic strategies. , 2022, Seminars in immunology.

[2]  G. De Palo,et al.  Airway myeloperoxidase (MPO) is associated with increased risk of exacerbations in COPD , 2022, 03.02 - Airway cell biology and immunopathology.

[3]  J. Tanus-Santos,et al.  Matrix Metalloproteinases on Severe COVID-19 Lung Disease Pathogenesis: Cooperative Actions of MMP-8/MMP-2 Axis on Immune Response through HLA-G Shedding and Oxidative Stress , 2022, Biomolecules.

[4]  B. Alisjahbana,et al.  Neutrophils and lymphocytes in relation to MMP-8 and MMP-9 levels in pulmonary tuberculosis and HIV co-infection , 2022, Journal of clinical tuberculosis and other mycobacterial diseases.

[5]  S. Charalambous,et al.  Major Neutrophil-Derived Soluble Mediators Associate With Baseline Lung Pathology and Post-Treatment Recovery in Tuberculosis Patients , 2021, Frontiers in Immunology.

[6]  T. Sterling,et al.  Elevated Plasma Matrix Metalloproteinase 8 Associates With Sputum Culture Positivity in Pulmonary Tuberculosis , 2021, medRxiv.

[7]  T. Scriba,et al.  Effect of Inflammatory Cytokines/Chemokines on Pulmonary Tuberculosis Culture Conversion and Disease Severity in HIV-Infected and -Uninfected Individuals From South Africa , 2021, Frontiers in Immunology.

[8]  L. McKinnon,et al.  Plasma Biomarkers of Risk of Tuberculosis Recurrence in HIV Co-Infected Patients From South Africa , 2021, Frontiers in Immunology.

[9]  Ronald Anderson,et al.  Interactions of HIV and Antiretroviral Therapy With Neutrophils and Platelets , 2021, Frontiers in Immunology.

[10]  H. McShane,et al.  Local Pulmonary Immunological Biomarkers in Tuberculosis , 2021, Frontiers in Immunology.

[11]  N. Ford,et al.  HIV-associated tuberculosis , 2021, International journal of STD & AIDS.

[12]  M. Campos,et al.  Cigarette smoke induction of S100A9 contributes to chronic obstructive pulmonary disease. , 2020, American journal of physiology. Lung cellular and molecular physiology.

[13]  J. Sutherland,et al.  Neutrophils in Tuberculosis-Associated Inflammation and Lung Pathology , 2020, Frontiers in Immunology.

[14]  M. Hoelscher,et al.  Development of chronic lung impairment in Mozambican TB patients and associated risks , 2020, BMC Pulmonary Medicine.

[15]  K. Dheda,et al.  Comparison of Xpert MTB/RIF (G4) and Xpert Ultra, including trace readouts, for the diagnosis of pulmonary tuberculosis in a TB and HIV endemic setting. , 2020, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[16]  S. Babu,et al.  Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases Are Potential Biomarkers of Pulmonary and Extra-Pulmonary Tuberculosis , 2020, Frontiers in Immunology.

[17]  Maqsood Ahmad,et al.  GeneXpert Technology for the diagnosis of HIV-associated tuberculosis: Is scale-up worth it? , 2020, Open life sciences.

[18]  W. Wong,et al.  Immune Biomarkers for Diagnosis and Treatment Monitoring of Tuberculosis: Current Developments and Future Prospects , 2019, Front. Microbiol..

[19]  V. Viswanathan,et al.  Plasma chemokines are biomarkers of disease severity, higher bacterial burden and delayed sputum culture conversion in pulmonary tuberculosis , 2019, Scientific Reports.

[20]  M. L. La Manna,et al.  Mycobacterium tuberculosis Drives Expansion of Low-Density Neutrophils Equipped With Regulatory Activities , 2019, Front. Immunol..

[21]  Nandini Dendukuri,et al.  Xpert MTB/RIF and Xpert MTB/RIF Ultra for pulmonary tuberculosis and rifampicin resistance in adults , 2019, The Cochrane database of systematic reviews.

[22]  S. Niemann,et al.  TB sequel: incidence, pathogenesis and risk factors of long-term medical and social sequelae of pulmonary TB – a study protocol , 2019, BMC Pulmonary Medicine.

[23]  V. Viswanathan,et al.  Elevated levels of matrix metalloproteinases reflect severity and extent of disease in tuberculosis-diabetes co-morbidity and are predominantly reversed following standard anti-tuberculosis or metformin treatment , 2018, BMC Infectious Diseases.

[24]  D. Weissman,et al.  Tuberculosis and lung damage: from epidemiology to pathophysiology , 2018, European Respiratory Review.

[25]  Justin M. Cohen,et al.  Disease Control Priorities, Third Edition (Volume 6): Major Infectious Diseases , 2017 .

[26]  V. Salomaa,et al.  Genetic Variants Contributing to Circulating Matrix Metalloproteinase 8 Levels and Their Association With Cardiovascular Diseases: A Genome-Wide Analysis , 2017, Circulation. Cardiovascular genetics.

[27]  R. Wilkinson,et al.  Neutrophil Activation and Enhanced Release of Granule Products in HIV-TB Immune Reconstitution Inflammatory Syndrome , 2017, Journal of acquired immune deficiency syndromes.

[28]  M. Segal,et al.  Biomarkers of Tuberculosis Severity and Treatment Effect: A Directed Screen of 70 Host Markers in a Randomized Clinical Trial , 2017, EBioMedicine.

[29]  J. M. Peyper,et al.  Matrix Degradation in Human Immunodeficiency Virus Type 1–Associated Tuberculosis and Tuberculosis Immune Reconstitution Inflammatory Syndrome: A Prospective Observational Study , 2017, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[30]  M. Pai,et al.  Tuberculosis Diagnostics: State of the Art and Future Directions. , 2016, Microbiology spectrum.

[31]  D. Weissman,et al.  Matrix Metalloproteinases in Tuberculosis-Immune Reconstitution Inflammatory Syndrome and Impaired Lung Function Among Advanced HIV/TB Co-infected Patients Initiating Antiretroviral Therapy , 2015, EBioMedicine.

[32]  A. Chaudhury,et al.  Mycobacterium tuberculosis infection in a HIV-positive patient , 2015, Respiratory medicine case reports.

[33]  JoAnne L. Flynn,et al.  Granzyme B‐expressing neutrophils correlate with bacterial load in granulomas from Mycobacterium tuberculosis‐infected cynomolgus macaques , 2015, Cellular microbiology.

[34]  J. Farrar,et al.  Tuberculosis in Adults and Children , 2015 .

[35]  J. Bruchfeld,et al.  Tuberculosis and HIV Coinfection. , 2015, Cold Spring Harbor perspectives in medicine.

[36]  R. Gilman,et al.  Neutrophil-Derived MMP-8 Drives AMPK-Dependent Matrix Destruction in Human Pulmonary Tuberculosis , 2015, PLoS pathogens.

[37]  A. M. Houghton.  Matrix metalloproteinases in destructive lung disease. , 2015, Matrix biology : journal of the International Society for Matrix Biology.

[38]  M. Selman,et al.  S100A8/A9 proteins mediate neutrophilic inflammation and lung pathology during tuberculosis. , 2013, American journal of respiratory and critical care medicine.

[39]  D. Douek,et al.  Systemic effects of inflammation on health during chronic HIV infection. , 2013, Immunity.

[40]  A. O’Garra,et al.  Systems approaches to studying the immune response in tuberculosis. , 2013, Current opinion in immunology.

[41]  A. Bernabé-Ortiz,et al.  Induced Sputum MMP-1, -3 & -8 Concentrations during Treatment of Tuberculosis , 2013, PloS one.

[42]  B. Corleis,et al.  Escape of Mycobacterium tuberculosis from oxidative killing by neutrophils , 2012, Cellular microbiology.

[43]  M. S. Fernández-García,et al.  MMP-8 Deficiency Increases TLR/RAGE Ligands S100A8 and S100A9 and Exacerbates Lung Inflammation during Endotoxemia , 2012, PloS one.

[44]  C. Gray,et al.  Effect of Standard Tuberculosis Treatment on Plasma Cytokine Levels in Patients with Active Pulmonary Tuberculosis , 2012, PloS one.

[45]  Alimuddin Zumla,et al.  Immunological biomarkers of tuberculosis , 2011, Nature Reviews Immunology.

[46]  C. K. Kwan,et al.  HIV and Tuberculosis: a Deadly Human Syndemic , 2011, Clinical Microbiology Reviews.

[47]  Paul M Kelly,et al.  A simple, valid, numerical score for grading chest x-ray severity in adult smear-positive pulmonary tuberculosis , 2010, Thorax.

[48]  F. Al-Zamel.  Detection and diagnosis of Mycobacterium tuberculosis , 2009, Expert review of anti-infective therapy.

[49]  M. Lederman,et al.  Microbial translocation is a cause of systemic immune activation in chronic HIV infection , 2006, Nature Medicine.

[50]  W. V. de Souza,et al.  Radiographic features of pulmonary tuberculosis in patients infected by HIV: is there an objective indicator of co-infection? , 2001, Revista da Sociedade Brasileira de Medicina Tropical.

[51]  L. Haramati,et al.  Effect of HIV status on chest radiographic and CT findings in patients with tuberculosis. , 1997, Clinical radiology.

[52]  Pranveer Singh,et al.  Diagnosis of TB: From conventional to modern molecular protocols. , 2019, Frontiers in bioscience.

[53]  R. Wilkinson,et al.  HIV-1 and the immune response to TB. , 2013, Future virology.