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RESEARCH ARTICLE

Gender-Dependent Differences in Plasma Matrix Metalloproteinase-8 Elevated in Pulmonary Tuberculosis Tarangini Sathyamoorthy1, Gurjinder Sandhu1, Liku B. Tezera2, Richard Thomas3, Akul Singhania2, Christopher H. Woelk2, Borislav D. Dimitrov2,4, Dan Agranoff1,5, Carlton A. W. Evans1,6, Jon S. Friedland1, Paul T. Elkington1,2,7*

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1 Infectious Diseases and Immunity, Imperial College London, London, United Kingdom, 2 NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom, 3 The Royal London Hospital, Whitechapel, United Kingdom, 4 Primary Care and Population Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom, 5 Brighton and Sussex University Hospitals NHS Trust, Brighton, United Kingdom, 6 Microbiology, Universidad Cayetano Heredia, Lima, Peru, 7 Institute for Life Sciences, University of Southampton, Southampton, United Kingdom * [email protected]

OPEN ACCESS Citation: Sathyamoorthy T, Sandhu G, Tezera LB, Thomas R, Singhania A, Woelk CH, et al. (2015) Gender-Dependent Differences in Plasma Matrix Metalloproteinase-8 Elevated in Pulmonary Tuberculosis. PLoS ONE 10(1): e0117605. doi:10.1371/journal.pone.0117605 Academic Editor: Yves St-Pierre, INRS, CANADA Received: June 10, 2014 Accepted: December 29, 2014 Published: January 30, 2015 Copyright: © 2015 Sathyamoorthy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: TS was funded by an MRC and GS by a Wellcome Clinical Research training fellowship. PE and JSF are grateful for support from the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) funding scheme at Imperial College. The authors are grateful for support from the Imperial College Healthcare Charity. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Abstract Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrix metalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TB but have not been comprehensively studied in plasma, nor have gender differences been investigated. We measured the plasma concentrations of MMPs in a carefully characterised, prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1 and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls, and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 was TB-specific (p