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

Moreira-Teixeira, L; Stimpson, P J; Stavropoulos, E; Hadebe, S; Chakravarty, P; Ioannou, M; Aramburu, I V; Herbert, E; Priestnall, S L; Suarez-Bonnet, A; Sousa, J; Fonseca, K L; Wang, Q; Vashakidze, S; Rodríguez-Martínez, P; Vilaplana, C; Saraiva, M; Papayannopoulos, V; O’Garra, A

Authors

L Moreira-Teixeira

P J Stimpson

E Stavropoulos

S Hadebe

P Chakravarty

M Ioannou

I V Aramburu

E Herbert

S L Priestnall

A Suarez-Bonnet

J Sousa

K L Fonseca

Q Wang

S Vashakidze

P Rodríguez-Martínez

C Vilaplana

M Saraiva

V Papayannopoulos

A O’Garra



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.

Citation

Moreira-Teixeira, L., Stimpson, P. J., Stavropoulos, E., Hadebe, S., Chakravarty, P., Ioannou, M., …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), 5566. https://doi.org/10.1038/s41467-020-19412-6

Journal Article Type Article
Acceptance Date Oct 12, 2020
Publication Date Nov 4, 2020
Deposit Date Nov 6, 2020
Publicly Available Date Nov 6, 2020
Journal Nature Communications
Publisher Nature Research
Peer Reviewed Peer Reviewed
Volume 11
Issue 1
Pages 5566
DOI https://doi.org/10.1038/s41467-020-19412-6
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
Public URL https://rvc-repository.worktribe.com/output/1374881

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