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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Neutrophil degranulation, NETosis and platelet degranulation pathway genes are co-induced in whole blood up to six months before tuberculosis diagnosis
PLoS ONE, Volume 17, No. 12 December, Article e0278295, Year 2022
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Description
Mycobacterium tuberculosis (M.tb) causes tuberculosis (TB) and remains one of the leading causes of mortality due to an infectious pathogen. Host immune responses have been implicated in driving the progression from infection to severe lung disease. We analyzed longitudinal RNA sequencing (RNAseq) data from the whole blood of 74 TB progressors whose samples were grouped into four six-month intervals preceding diagnosis (the GC6-74 study). We additionally analyzed RNAseq data from an independent cohort of 90 TB patients with positron emission tomography-computed tomography (PET-CT) scan results which were used to categorize them into groups with high and low levels of lung damage (the Catalysis TB Biomarker study). These groups were compared to non-TB controls to obtain a complete whole blood transcriptional profile for individuals spanning from early stages of M.tb infection to TB diagnosis. The results revealed a steady increase in the number of genes that were differentially expressed in progressors at time points closer to diagnosis with 278 genes at 13-18 months, 742 at 7-12 months and 5, 131 detected 1-6 months before diagnosis and 9, 205 detected in TB patients. A total of 2, 144 differentially expressed genes were detected when comparing TB patients with high and low levels of lung damage. There was a large overlap in the genes upregulated in progressors 1-6 months before diagnosis (86%) with those in TB patients. A comprehensive pathway analysis revealed a potent activation of neutrophil and platelet mediated defenses including neutrophil and platelet degranulation, and NET formation at both time points. These pathways were also enriched in TB patients with high levels of lung damage compared to those with low. These findings suggest that neutrophils and platelets play a critical role in TB pathogenesis, and provide details of the timing of specific effector mechanisms that may contribute to TB lung pathology. Copyright: © 2022 Meier 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.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC9714760/bin/pone.0278295.s001.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC9714760/bin/pone.0278295.s002.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC9714760/bin/pone.0278295.s003.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC9714760/bin/pone.0278295.s004.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC9714760/bin/pone.0278295.s005.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC9714760/bin/pone.0278295.s006.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC9714760/bin/pone.0278295.s007.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC9714760/bin/pone.0278295.s008.docx
Authors & Co-Authors
Meier, Stuart K.
South Africa, Stellenbosch
Stellenbosch University
South Africa, Pretoria
National Research Foundation
South Africa, Tygerberg
South African Medical Research Council
Seddon, James Alexander
South Africa, Stellenbosch
Stellenbosch University
United Kingdom, London
Imperial College London
Maasdorp, Elizna
South Africa, Stellenbosch
Stellenbosch University
South Africa, Pretoria
National Research Foundation
South Africa, Tygerberg
South African Medical Research Council
Kleynhans, Léanie
South Africa, Stellenbosch
Stellenbosch University
South Africa, Pretoria
National Research Foundation
South Africa, Tygerberg
South African Medical Research Council
Du Plessis, Nelita M.
South Africa, Stellenbosch
Stellenbosch University
South Africa, Pretoria
National Research Foundation
South Africa, Tygerberg
South African Medical Research Council
Loxton, A. G.
South Africa, Stellenbosch
Stellenbosch University
South Africa, Pretoria
National Research Foundation
South Africa, Tygerberg
South African Medical Research Council
Malherbe, Stephanus T.
South Africa, Stellenbosch
Stellenbosch University
South Africa, Pretoria
National Research Foundation
South Africa, Tygerberg
South African Medical Research Council
Zak, Daniel E.
United States, Seattle
Children's Hospital and Regional Medical Center
Thompson, Ethan G.
United States, Seattle
Children's Hospital and Regional Medical Center
Duffy, Fergal J.
United States, Seattle
Children's Hospital and Regional Medical Center
Kaufmann, Stefan H.E.
Germany, Berlin
Max Planck Institute for Infection Biology
United States, College Station
Texas A&m University
Ottenhoff, Tom H.M.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Scriba, Thomas Jens
South Africa, Cape Town
University of Cape Town
Suliman, Sara A.
South Africa, Cape Town
University of Cape Town
Sutherland, Jayne S.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Winter, Jill
United States, San Ramon
Catalysis Foundation for Health
Kuivaniemi, Helena
South Africa, Stellenbosch
Stellenbosch University
South Africa, Pretoria
National Research Foundation
South Africa, Tygerberg
South African Medical Research Council
Walzl, Gerhard
South Africa, Stellenbosch
Stellenbosch University
South Africa, Pretoria
National Research Foundation
South Africa, Tygerberg
South African Medical Research Council
Tromp, Gerard C.
South Africa, Stellenbosch
Stellenbosch University
South Africa, Pretoria
National Research Foundation
South Africa, Tygerberg
South African Medical Research Council
Black, Gillian Frances
South Africa, Stellenbosch
Stellenbosch University
South Africa, Pretoria
National Research Foundation
South Africa, Tygerberg
South African Medical Research Council
Van Der Spuy, Gian D.
South Africa, Stellenbosch
Stellenbosch University
South Africa, Pretoria
National Research Foundation
South Africa, Tygerberg
South African Medical Research Council
Stanley, Kim
South Africa, Stellenbosch
Stellenbosch University
South Africa, Pretoria
National Research Foundation
South Africa, Tygerberg
South African Medical Research Council
Kriel, Magdalena
South Africa, Stellenbosch
Stellenbosch University
South Africa, Pretoria
National Research Foundation
South Africa, Tygerberg
South African Medical Research Council
Nene, Nonhlanhla F.
South Africa, Stellenbosch
Stellenbosch University
South Africa, Pretoria
National Research Foundation
South Africa, Tygerberg
South African Medical Research Council
Roberts, Teri R.
South Africa, Stellenbosch
Stellenbosch University
South Africa, Pretoria
National Research Foundation
South Africa, Tygerberg
South African Medical Research Council
Gutschmidt, Andrea
South Africa, Stellenbosch
Stellenbosch University
South Africa, Pretoria
National Research Foundation
South Africa, Tygerberg
South African Medical Research Council
Smith, Bronwyn
South Africa, Stellenbosch
Stellenbosch University
South Africa, Pretoria
National Research Foundation
South Africa, Tygerberg
South African Medical Research Council
Chegou, Novel N.
South Africa, Stellenbosch
Stellenbosch University
South Africa, Pretoria
National Research Foundation
South Africa, Tygerberg
South African Medical Research Council
Tabb, David L.
South Africa, Stellenbosch
Stellenbosch University
South Africa, Pretoria
National Research Foundation
South Africa, Tygerberg
South African Medical Research Council
Klein, Michèl R.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Haks, Mariëlle C.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Franken, Kees L.M.C.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Geluk, Annemieke
Netherlands, Leiden
Leids Universitair Medisch Centrum
van Meijgaarden, Krista E.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Henry Boom, W.
United States, Cleveland
University Hospitals Case Medical Center
Thiel, Bonnie A.
United States, Cleveland
University Hospitals Case Medical Center
Mayanja-Kizza, Harriet
Uganda, Kampala
Makerere University
Joloba, Moses Lutaakome
Uganda, Kampala
Makerere University
Zalwango, Sarah K.
Uganda, Kampala
Makerere University
Nsereko, Mary
Uganda, Kampala
Makerere University
Okwera, Brenda
Uganda, Kampala
Makerere University
Kisingo, Hussein
Uganda, Kampala
Makerere University
Parida, Shreemanta K.
Germany, Berlin
Max Planck Institute for Infection Biology
Golinski, Robert
Germany, Berlin
Max Planck Institute for Infection Biology
Maertzdorf, Jeroen
Germany, Berlin
Max Planck Institute for Infection Biology
Weiner, January Mikolaj
Germany, Berlin
Max Planck Institute for Infection Biology
Jacobson, Marc
Germany, Berlin
Max Planck Institute for Infection Biology
Dockrell, Hazel M.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Lalor, Maeve K.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Smith, Steven G.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Gorak-Stolinska, Patricia M.A.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Hur, Yun-gyoung
United Kingdom, London
London School of Hygiene & Tropical Medicine
Lee, Ji-sook
United Kingdom, London
London School of Hygiene & Tropical Medicine
Crampin, Amelia Catharine
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
French, Neil
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Ngwira, Bagrey M.M.
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Ben-Smith, Anne W.
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Watkins, Kate
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Ambrose, Lyn R.
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Simukonda, Felanji D.
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Mvula, Hazzie
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Chilongo, Femia
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Saul, Jacky
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Branson, Keith
Malawi, Chilumba
Malawi Epidemiology and Intervention Research Unit
Mahomed, Hassan
South Africa, Cape Town
University of Cape Town
Jane Hughes, E.
South Africa, Cape Town
University of Cape Town
Bilek, Nicole
South Africa, Cape Town
University of Cape Town
Erasmus, Mzwandile
South Africa, Cape Town
University of Cape Town
Xasa, Onke
South Africa, Cape Town
University of Cape Town
Veldsman, Ashley
South Africa, Cape Town
University of Cape Town
Downing, Katrina J.
South Africa, Cape Town
University of Cape Town
Fisher, Michelle L.
South Africa, Cape Town
University of Cape Town
Penn-Nicholson, Adam
South Africa, Cape Town
University of Cape Town
Mulenga, Humphrey
South Africa, Cape Town
University of Cape Town
Abel, Brian
South Africa, Cape Town
University of Cape Town
Bowmaker, Mark
South Africa, Cape Town
University of Cape Town
M Kagina, Benjamin Mugo N.
South Africa, Cape Town
University of Cape Town
Chung, William Kwong
South Africa, Cape Town
University of Cape Town
Hanekom, Willem A.
South Africa, Cape Town
University of Cape Town
Sadoff, Jerald C.
United States, Rockville
Aeras
Sizemore, Donata R.
United States, Rockville
Aeras
Ramachandran, S.
United States, Rockville
Aeras
Barker, Lew F.
United States, Rockville
Aeras
Brennan, Michael James
United States, Rockville
Aeras
Weichold, Frank F.
United States, Rockville
Aeras
Muller, Stefanie
United States, Rockville
Aeras
Geiter, Lawrence J.
United States, Rockville
Aeras
Kassa, Desta
Ethiopia, Addis Ababa
Ethiopian Public Health Institute
Abebe, Almaz
Ethiopia, Addis Ababa
Ethiopian Public Health Institute
Mesele, Tsehayenesh
Ethiopia, Addis Ababa
Ethiopian Public Health Institute
Tegbaru, Belete
Ethiopia, Addis Ababa
Ethiopian Public Health Institute
van Baarle, Debbie
Netherlands, Utrecht
University Medical Center Utrecht
Miedema, Frank F.
Netherlands, Utrecht
University Medical Center Utrecht
Howe, Rawleigh Craig
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Mihret, Adane
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Aseffa, Abraham
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Bekele, Yonas Y.
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Iwnetu, Rachel
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Tafesse, Mesfin
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Yamuah, Lawrence K.
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Ota, Martin Okechukwu C.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Hill, Philip C.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Adegbola, Richard A.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Corrah, Tumani P.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Antonio, Martin
United Kingdom, London
London School of Hygiene & Tropical Medicine
Togun, Toyin Omotayo
United Kingdom, London
London School of Hygiene & Tropical Medicine
Adetifa, Ifedayo
United Kingdom, London
London School of Hygiene & Tropical Medicine
Donkor, Simon A.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Skyt Andersen, Paal Skytt
Denmark, Copenhagen
Statens Serum Institut
Rosenkrands, Ida
Denmark, Copenhagen
Statens Serum Institut
Doherty, Timothy Mark
Denmark, Copenhagen
Statens Serum Institut
Weldingh, Karin N.
Denmark, Copenhagen
Statens Serum Institut
Schoolnik, Gary K.
United States, Palo Alto
Stanford University
Dolganov, Gregory M.
United States, Palo Alto
Stanford University
Van, Tran T.
United States, Palo Alto
Stanford University
Dupont, Patrick
Belgium, Leuven
Ku Leuven
South Africa, Stellenbosch
Stellenbosch University
Kant, Ilse
South Africa, Stellenbosch
Stellenbosch University
Ronacher, Katharina
South Africa, Pretoria
National Research Foundation
Chen, Ray Y.
United States, Bethesda
National Institutes of Health Nih
Via, L. E.
United States, Bethesda
National Institutes of Health Nih
South Africa, Cape Town
Wellcome Centre for Infectious Diseases Research in Africa
Thienemann, Friedrich
South Africa, Cape Town
Wellcome Centre for Infectious Diseases Research in Africa
South Africa, Cape Town
University of Cape Town
Wilkinson, Robert John
South Africa, Cape Town
Wellcome Centre for Infectious Diseases Research in Africa
South Africa, Cape Town
University of Cape Town
United Kingdom, London
The Francis Crick Institute
United Kingdom, London
Imperial College London
Barry, Clifton Earl
South Africa, Pretoria
National Research Foundation
United States, Bethesda
National Institutes of Health Nih
South Africa, Cape Town
Wellcome Centre for Infectious Diseases Research in Africa
Griffith-Richards, Stephanie Barbara
South Africa, Stellenbosch
Stellenbosch University
Ellman, Annare
South Africa, Stellenbosch
Stellenbosch University
Beltran, Caroline G.G.
South Africa, Pretoria
National Research Foundation
Thiart, Lani
South Africa, Pretoria
National Research Foundation
Lucas, Lance A.
South Africa, Pretoria
National Research Foundation
Alland, David
United States, Newark
Rutgers Biomedical and Health Sciences
Shenai, Shubhada V.
United States, Newark
Rutgers Biomedical and Health Sciences
Dodd, Lori Elizabeth
United States, Bethesda
National Institutes of Health Nih
Warwick, James M.
South Africa, Stellenbosch
Stellenbosch University
Statistics
Citations: 6
Authors: 132
Affiliations: 25
Identifiers
Doi:
10.1371/journal.pone.0278295
ISSN:
19326203
Research Areas
Environmental
Health System And Policy
Infectious Diseases
Study Design
Cohort Study