Major Neutrophil-Derived Soluble Mediators Associate With Baseline Lung Pathology and Post-Treatment Recovery in Tuberculosis Patients

BackgroundThe inflammatory response to Mycobacterium tuberculosis results in variable degrees of lung pathology during active TB (ATB) with central involvement of neutrophils. Little is known about neutrophil-derived mediators and their role in disease severity at baseline and recovery upon TB treat...

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Autores principales:	Caleb Nwongbouwoh Muefong, Olumuyiwa Owolabi, Simon Donkor, Salome Charalambous, Joseph Mendy, Isatou C. M. Sey, Abhishek Bakuli, Andrea Rachow, Christof Geldmacher, Jayne S. Sutherland
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	tuberculosis neutrophils myeloperoxidase S100A8/9 MMP8 lung pathology Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/0c7071691b8a419991d0a4a023eb58fa
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spelling	oai:doaj.org-article:0c7071691b8a419991d0a4a023eb58fa2021-11-30T14:37:44ZMajor Neutrophil-Derived Soluble Mediators Associate With Baseline Lung Pathology and Post-Treatment Recovery in Tuberculosis Patients1664-322410.3389/fimmu.2021.740933https://doaj.org/article/0c7071691b8a419991d0a4a023eb58fa2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.740933/fullhttps://doaj.org/toc/1664-3224BackgroundThe inflammatory response to Mycobacterium tuberculosis results in variable degrees of lung pathology during active TB (ATB) with central involvement of neutrophils. Little is known about neutrophil-derived mediators and their role in disease severity at baseline and recovery upon TB treatment initiation.Methods107 adults with confirmed pulmonary TB were categorised based on lung pathology at baseline and following successful therapy using chest X-ray scores (Ralph scores) and GeneXpert bacterial load (Ct values). Plasma, sputum, and antigen-stimulated levels of MMP1, MMP3, MMP8, MMP9, MPO, S100A8/9, IL8, IL10, IL12/23(p40), GM-CSF, IFNγ, and TNF were analysed using multiplex cytokine arrays.ResultsAt baseline, neutrophil counts correlated with plasma levels of MMP8 (rho = 0.45, p = 2.80E−06), S100A8 (rho = 0.52, p = 3.00E−08) and GM-CSF (rho = 0.43, p = 7.90E−06). Levels of MMP8 (p = 3.00E−03), MMP1 (p = 1.40E−02), S100A8 (p = 1.80E−02) and IL12/23(p40) (p = 1.00E−02) were associated with severe lung damage, while sputum MPO levels were directly linked to lung damage (p = 1.80E−03), Mtb load (p = 2.10E−02) and lung recovery (p = 2.40E−02). Six months of TB therapy significantly decreased levels of major neutrophil-derived pro-inflammatory mediators: MMP1 (p = 4.90E−12 and p = 2.20E−07), MMP8 (p = 3.40E−14 and p = 1.30E−05) and MMP9 (p = 1.60E−04 and p = 1.50E−03) in plasma and sputum, respectively. Interestingly, following H37Rv whole cell lysate stimulation, S100A8 (p = 2.80E−02), MMP9 (p = 3.60E−02) and MPO (p = 9.10E−03) levels at month 6 were significantly higher compared to baseline. Sputum MMP1 (p = 1.50E−03), MMP3 (p = 7.58E−04), MMP9 (p = 2.60E−02) and TNF (p = 3.80E−02) levels were lower at month 6 compared to baseline in patients with good lung recovery.ConclusionIn this study, patients with severe lung pathology at baseline and persistent lung damage after treatment were associated with higher plasma and sputum levels of major pro-inflammatory neutrophil-derived mediators. Interestingly, low sputum MPO levels were associated with severe lung damage, higher Mtb burden and low recovery. Our data suggest that therapeutic agents which target these mediators should be considered for future studies on biomarkers and host-directed therapeutic approaches against TB-related lung pathology and/or lung recovery.Caleb Nwongbouwoh MuefongCaleb Nwongbouwoh MuefongOlumuyiwa OwolabiSimon DonkorSalome CharalambousJoseph MendyIsatou C. M. SeyAbhishek BakuliAbhishek BakuliAndrea RachowAndrea RachowChristof GeldmacherChristof GeldmacherJayne S. SutherlandFrontiers Media S.A.articletuberculosisneutrophilsmyeloperoxidaseS100A8/9MMP8lung pathologyImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tuberculosis neutrophils myeloperoxidase S100A8/9 MMP8 lung pathology Immunologic diseases. Allergy RC581-607
spellingShingle	tuberculosis neutrophils myeloperoxidase S100A8/9 MMP8 lung pathology Immunologic diseases. Allergy RC581-607 Caleb Nwongbouwoh Muefong Caleb Nwongbouwoh Muefong Olumuyiwa Owolabi Simon Donkor Salome Charalambous Joseph Mendy Isatou C. M. Sey Abhishek Bakuli Abhishek Bakuli Andrea Rachow Andrea Rachow Christof Geldmacher Christof Geldmacher Jayne S. Sutherland Major Neutrophil-Derived Soluble Mediators Associate With Baseline Lung Pathology and Post-Treatment Recovery in Tuberculosis Patients
description	BackgroundThe inflammatory response to Mycobacterium tuberculosis results in variable degrees of lung pathology during active TB (ATB) with central involvement of neutrophils. Little is known about neutrophil-derived mediators and their role in disease severity at baseline and recovery upon TB treatment initiation.Methods107 adults with confirmed pulmonary TB were categorised based on lung pathology at baseline and following successful therapy using chest X-ray scores (Ralph scores) and GeneXpert bacterial load (Ct values). Plasma, sputum, and antigen-stimulated levels of MMP1, MMP3, MMP8, MMP9, MPO, S100A8/9, IL8, IL10, IL12/23(p40), GM-CSF, IFNγ, and TNF were analysed using multiplex cytokine arrays.ResultsAt baseline, neutrophil counts correlated with plasma levels of MMP8 (rho = 0.45, p = 2.80E−06), S100A8 (rho = 0.52, p = 3.00E−08) and GM-CSF (rho = 0.43, p = 7.90E−06). Levels of MMP8 (p = 3.00E−03), MMP1 (p = 1.40E−02), S100A8 (p = 1.80E−02) and IL12/23(p40) (p = 1.00E−02) were associated with severe lung damage, while sputum MPO levels were directly linked to lung damage (p = 1.80E−03), Mtb load (p = 2.10E−02) and lung recovery (p = 2.40E−02). Six months of TB therapy significantly decreased levels of major neutrophil-derived pro-inflammatory mediators: MMP1 (p = 4.90E−12 and p = 2.20E−07), MMP8 (p = 3.40E−14 and p = 1.30E−05) and MMP9 (p = 1.60E−04 and p = 1.50E−03) in plasma and sputum, respectively. Interestingly, following H37Rv whole cell lysate stimulation, S100A8 (p = 2.80E−02), MMP9 (p = 3.60E−02) and MPO (p = 9.10E−03) levels at month 6 were significantly higher compared to baseline. Sputum MMP1 (p = 1.50E−03), MMP3 (p = 7.58E−04), MMP9 (p = 2.60E−02) and TNF (p = 3.80E−02) levels were lower at month 6 compared to baseline in patients with good lung recovery.ConclusionIn this study, patients with severe lung pathology at baseline and persistent lung damage after treatment were associated with higher plasma and sputum levels of major pro-inflammatory neutrophil-derived mediators. Interestingly, low sputum MPO levels were associated with severe lung damage, higher Mtb burden and low recovery. Our data suggest that therapeutic agents which target these mediators should be considered for future studies on biomarkers and host-directed therapeutic approaches against TB-related lung pathology and/or lung recovery.
format	article
author	Caleb Nwongbouwoh Muefong Caleb Nwongbouwoh Muefong Olumuyiwa Owolabi Simon Donkor Salome Charalambous Joseph Mendy Isatou C. M. Sey Abhishek Bakuli Abhishek Bakuli Andrea Rachow Andrea Rachow Christof Geldmacher Christof Geldmacher Jayne S. Sutherland
author_facet	Caleb Nwongbouwoh Muefong Caleb Nwongbouwoh Muefong Olumuyiwa Owolabi Simon Donkor Salome Charalambous Joseph Mendy Isatou C. M. Sey Abhishek Bakuli Abhishek Bakuli Andrea Rachow Andrea Rachow Christof Geldmacher Christof Geldmacher Jayne S. Sutherland
author_sort	Caleb Nwongbouwoh Muefong
title	Major Neutrophil-Derived Soluble Mediators Associate With Baseline Lung Pathology and Post-Treatment Recovery in Tuberculosis Patients
title_short	Major Neutrophil-Derived Soluble Mediators Associate With Baseline Lung Pathology and Post-Treatment Recovery in Tuberculosis Patients
title_full	Major Neutrophil-Derived Soluble Mediators Associate With Baseline Lung Pathology and Post-Treatment Recovery in Tuberculosis Patients
title_fullStr	Major Neutrophil-Derived Soluble Mediators Associate With Baseline Lung Pathology and Post-Treatment Recovery in Tuberculosis Patients
title_full_unstemmed	Major Neutrophil-Derived Soluble Mediators Associate With Baseline Lung Pathology and Post-Treatment Recovery in Tuberculosis Patients
title_sort	major neutrophil-derived soluble mediators associate with baseline lung pathology and post-treatment recovery in tuberculosis patients
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/0c7071691b8a419991d0a4a023eb58fa
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Major Neutrophil-Derived Soluble Mediators Associate With Baseline Lung Pathology and Post-Treatment Recovery in Tuberculosis Patients

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