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      Elevated Plasma Matrix Metalloproteinase 8 Associates With Sputum Culture Positivity in Pulmonary Tuberculosis  

      brief-report

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          Abstract

          Current methods for tuberculosis treatment monitoring are suboptimal. We evaluated plasma matrix metalloproteinase (MMP) and procollagen III N-terminal propeptide concentrations before and during tuberculosis treatment as biomarkers. Plasma MMP-1, MMP-8, and MMP-10 concentrations significantly decreased during treatment. Plasma MMP-8 was increased in sputum Mycobacterium tuberculosis culture–positive relative to culture-negative participants, before (median, 4993 pg/mL [interquartile range, 2542–9188] vs 698 [218–4060] pg/mL, respectively; P = .004) and after (3650 [1214–3888] vs 720 [551–1321] pg/mL; P = .008) 6 months of tuberculosis treatment. Consequently, plasma MMP-8 is a potential biomarker to enhance tuberculosis treatment monitoring and screen for possible culture positivity.

          Abstract

          In this cohort study, plasma matrix metalloproteinase 8 was increased in sputum culture–positive participants at tuberculosis diagnosis and after 6 months of tuberculosis treatment, demonstrating its potential as a biomarker of sputum culture positivity, to enhance tuberculosis treatment monitoring.

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          Neutrophil-Derived MMP-8 Drives AMPK-Dependent Matrix Destruction in Human Pulmonary Tuberculosis

          Catherine Ong, Paul T. Elkington, Sara Brilha … (2015)
          Pulmonary cavities, the hallmark of tuberculosis (TB), are characterized by high mycobacterial load and perpetuate the spread of M. tuberculosis. The mechanism of matrix destruction resulting in cavitation is not well defined. Neutrophils are emerging as key mediators of TB immunopathology and their influx are associated with poor outcomes. We investigated neutrophil-dependent mechanisms involved in TB-associated matrix destruction using a cellular model, a cohort of 108 patients, and in separate patient lung biopsies. Neutrophil-derived NF-kB-dependent matrix metalloproteinase-8 (MMP-8) secretion was up-regulated in TB and caused matrix destruction both in vitro and in respiratory samples of TB patients. Collagen destruction induced by TB infection was abolished by doxycycline, a licensed MMP inhibitor. Neutrophil extracellular traps (NETs) contain MMP-8 and are increased in samples from TB patients. Neutrophils lined the circumference of human pulmonary TB cavities and sputum MMP-8 concentrations reflected TB radiological and clinical disease severity. AMPK, a central regulator of catabolism, drove neutrophil MMP-8 secretion and neutrophils from AMPK-deficient patients secrete lower MMP-8 concentrations. AMPK-expressing neutrophils are present in human TB lung biopsies with phospho-AMPK detected in nuclei. These data demonstrate that neutrophil-derived MMP-8 has a key role in the immunopathology of TB and is a potential target for host-directed therapy in this infectious disease.
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            Metalloproteinases and their natural inhibitors in inflammation and immunity.

            Ashley Weiss, Sankriti Murthy, Rama Khokha (2013)
            Over the past 50 years, steady growth in the field of metalloproteinase biology has shown that the degradation of extracellular matrix components represents only a fraction of the functions performed by these enzymes and has highlighted their fundamental roles in immunity. Metalloproteinases regulate aspects of immune cell development, effector function, migration and ligand-receptor interactions. They carry out ectodomain shedding of cytokines and their cognate receptors. Together with their endogenous inhibitors TIMPs (tissue inhibitor of metalloproteinases), these enzymes regulate signalling downstream of the tumour necrosis factor receptor and the interleukin-6 receptor, as well as that downstream of the epidermal growth factor receptor and Notch, which are all pertinent for inflammatory responses. This Review discusses the metalloproteinase family as a crucial component in immune cell development and function.
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              Global tuberculosis report 2022.

              World Organization, . World Health Organization, World Health Organization (2021)
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                Author and article information

                Contributors
                N F Walker:
                ORCID: https://orcid.org/0000-0002-3345-7694
                F Karim
                M Y S Moosa
                S Moodley
                M Mazibuko
                K Khan
                T R Sterling
                Y F van der Heijden
                A D Grant
                P T Elkington
                A Pym
                A Leslie
                Journal
                Journal ID (nlm-ta): J Infect Dis
                Journal ID (iso-abbrev): J Infect Dis
                Journal ID (publisher-id): jid
                Title: The Journal of Infectious Diseases
                Publisher: Oxford University Press
                ISSN (Print): 0022-1899
                ISSN (Electronic): 1537-6613
                Publication date Collection: 01 September 2022
                Publication date (Electronic): 01 May 2022
                Publication date PMC-release: 01 May 2022
                Volume: 226
                Issue: 5
                Pages: 928-932
                Affiliations
                Department of Clinical Sciences, Liverpool School of Tropical Medicine and Liverpool University Hospitals NHS Foundation Trust , Liverpool, United Kingdom
                TB Centre and Department of Clinical Research, London School of Hygiene and Tropical Medicine , London, United Kingdom
                Africa Health Research Institute , KwaZulu-Natal, South Africa
                Department of Infectious Diseases, University of KwaZulu-Natal , Durban, South Africa
                Africa Health Research Institute , KwaZulu-Natal, South Africa
                Africa Health Research Institute , KwaZulu-Natal, South Africa
                Africa Health Research Institute , KwaZulu-Natal, South Africa
                Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center , Nashville, Tennessee, USA
                Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center , Nashville, Tennessee, USA
                The Aurum Institute , Johannesburg, South Africa
                TB Centre and Department of Clinical Research, London School of Hygiene and Tropical Medicine , London, United Kingdom
                Africa Health Research Institute , KwaZulu-Natal, South Africa
                School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal , Durban, South Africa
                NIHR Biomedical Research Centre, Clinical and Experimental Sciences, University of Southampton , Southampton, United Kingdom
                Africa Health Research Institute , KwaZulu-Natal, South Africa
                Africa Health Research Institute , KwaZulu-Natal, South Africa
                School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal , Durban, South Africa
                Division of Infection and Immunity, University College London , London, United Kingdom
                Author notes

                Presented in part: 11th European Congress on Tropical Medicine and International Health, Liverpool, United Kingdom, 16–20 September 2019.

                Correspondence: N. F. Walker, Senior Clinical Lecturer, Department of Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, United Kingdom ( naomi.walker@ 123456lstmed.ac.uk ).

                Potential conflicts of interest . All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

                Author information
                https://orcid.org/0000-0002-3345-7694
                Article
                Publisher ID: jiac160
                DOI: 10.1093/infdis/jiac160
                PMC ID: 9470104
                PubMed ID: 35510939
                SO-VID: cf996fc6-1d75-4ab3-a775-224cb24476dc
                Copyright © © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 10 December 2021
                Date: 21 April 2022
                Date accepted : 28 April 2022
                Date: 24 June 2022
                Page count
                Pages: 5
                Categories
                Subject: Brief Report
                Subject: Bacteria
                Subject: AcademicSubjects/MED00290

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: tuberculosis,hiv,matrix metalloproteinase,procollagen iii n-terminal propeptide,diagnosis,immunopathology
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: tuberculosis, hiv, matrix metalloproteinase, procollagen iii n-terminal propeptide, diagnosis, immunopathology

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