Type I IFN exacerbates disease in tuberculosis-susceptible mice by inducing neutrophil-mediated lung inflammation and NETosis

Moreira-Teixeira, L and Stimpson, P J and Stavropoulos, E and Hadebe, S and Chakravarty, P and Ioannou, M and Aramburu, I V and Herbert, E and Priestnall, S L and Suarez-Bonnet, A and Sousa, J and Fonseca, K L and Wang, Q and Vashakidze, S and Rodríguez-Martínez, P and Vilaplana, C and Saraiva, M and Papayannopoulos, V and O’Garra, A (2020) Type I IFN exacerbates disease in tuberculosis-susceptible mice by inducing neutrophil-mediated lung inflammation and NETosis. Nature Communications, 11 (1). p. 5566. ISSN 2041-1723

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Abstract

Abstract: 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.

Item Type:	Article
RVC Publication Type:	Original research article
DOI:	https://doi.org/10.1038/s41467-020-19412-6
Uncontrolled Keywords:	Article, /631/250, /631/250/127, /631/250/254, /631/250/255, /631/250/256, /64/110, /14/63, /38/39, /38/91, /14/1, /13/31, article
Departments:	Comparative Biomedical Sciences
SWORD Depositor:	Publications Repository
Depositing User:	Publications Repository
Last Modified:	16 Feb 2021 13:31
URI:	https://researchonline.rvc.ac.uk/id/eprint/13231
Date Deposited:	6 November 2020

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