Type I IFN exacerbates disease in tuberculosis-susceptible mice by inducing neutrophil-mediated lung inflammation and NETosis
Moreira-Teixeira, Lúcia (The Francis Crick Institute, London)
Stimpson, Philippa J. (The Francis Crick Institute, London)
Stavropoulos, Evangelos (The Francis Crick Institute, London)
Hadebe, Sabelo (The Francis Crick Institute, London)
Chakravarty, Probir (The Francis Crick Institute, London)
Ioannou, Marianna (The Francis Crick Institute, London)
Aramburu, Iker Valle (The Francis Crick Institute, London)
Herbert, Eleanor (The Francis Crick Institute, London)
Priestnall, Simon L. (The Francis Crick Institute, London)
Suarez-Bonnet, Alejandro (The Francis Crick Institute, London)
Sousa, Jeremy (Universidade do Porto. ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Porto)
Fonseca, Kaori L. (Instituto Gulbenkian de Ciência (IGC), Oeiras)
Wang, Qian (The Francis Crick Institute, London)
Vashakidze, Sergo (National Center for Tuberculosis and Lung Diseases (NCTLD), Tbilisi)
Rodríguez-Martínez, Paula (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Vilaplana, Cristina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Saraiva, Margarida (Universidade do Porto. IBMC - Instituto de Biologia Molecular e Celular)
Papayannopoulos, Venizelos (The Francis Crick Institute, London)
O'Garra, Anne (Imperial College London)

Data:	2020
Resum:	Tuberculosis (TB) is a leading cause of mortality due to infectious disease, but the factors determining disease progression are unclear. Transcriptional signatures associated with type I IFN signalling and neutrophilic inflammation were shown to correlate with disease severity in mouse models of TB. Here we show that similar transcriptional signatures correlate with increased bacterial loads and exacerbate pathology during Mycobacterium tuberculosis infection upon GM-CSF blockade. Loss of GM-CSF signalling or genetic susceptibility to TB (C3HeB/FeJ mice) result in type I IFN-induced neutrophil extracellular trap (NET) formation that promotes bacterial growth and promotes disease severity. Consistently, NETs are present in necrotic lung lesions of TB patients responding poorly to antibiotic therapy, supporting the role of NETs in a late stage of TB pathogenesis. Our findings reveal an important cytokine-based innate immune effector network with a central role in determining the outcome of M. tuberculosis infection.
Ajuts:	Ministerio de Economía y Competitividad CP13/00174 Ministerio de Economía y Competitividad CPII18/00031 Ministerio de Economía y Competitividad PI16/01511
Nota:	This study was funded by The Francis Crick Institute which receives its core funding from Cancer Research UK (FC001126, FC001999, FC001129), the UK Medical Research Council (FC001126, FC001999, FC001129), and the Wellcome Trust (FC001126, FC001999, FC001129); before that by the UK Medical Research Council (MRC U117565642); and by the European Research Council (294682-TB-PATH). The collection of human lung tissue samples for this study was funded by the Spanish Government-FEDER Funds through CP13/00174, CPII18/00031 and PI16/01511 grants, and the CIBER Enfermedades Respiratorias Network; and by the Spanish Society of Pneumology and Thoracic Surgery (SEPAR) through grant 16/023.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Nature communications, Vol. 11 (november 2020) , ISSN 2041-1723

DOI: 10.1038/s41467-020-19412-6
PMID: 33149141

18 p, 7.7 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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