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Mouse transcriptome reveals potential signatures of protection and pathogenesis in human tuberculosis

Moreira-Teixeira, L; Tabone, O; Graham, C M; Singhania, A; Stavropoulos, E; Redford, P S; Chakravarty, P; Priestnall, S L; Suarez-Bonnet, A; Herbert, E; Mayer-Barber, K D; Sher, A; Fonseca, K L; Sousa, J; Cá, B; Verma, R; Haldar, P; Saraiva, M; O’Garra, A


L Moreira-Teixeira

O Tabone

C M Graham

A Singhania

E Stavropoulos

P S Redford

P Chakravarty

S L Priestnall

A Suarez-Bonnet

E Herbert

K D Mayer-Barber

A Sher

K L Fonseca

J Sousa

B Cá

R Verma

P Haldar

M Saraiva

A O’Garra


Although mouse infection models have been extensively used to study the host response to Mycobacterium tuberculosis, their validity in revealing determinants of human tuberculosis (TB) resistance and disease progression has been heavily debated. Here, we show that the modular transcriptional signature in the blood of susceptible mice infected with a clinical isolate of M. tuberculosis resembles that of active human TB disease, with dominance of a type I interferon response and neutrophil activation and recruitment, together with a loss in B lymphocyte, natural killer and T cell effector responses. In addition, resistant but not susceptible strains of mice show increased lung B cell, natural killer and T cell effector responses in the lung upon infection. Notably, the blood signature of active disease shared by mice and humans is also evident in latent TB progressors before diagnosis, suggesting that these responses both predict and contribute to the pathogenesis of progressive M. tuberculosis infection.


Moreira-Teixeira, L., Tabone, O., Graham, C. M., Singhania, A., Stavropoulos, E., Redford, P. S., …O’Garra, A. (2020). Mouse transcriptome reveals potential signatures of protection and pathogenesis in human tuberculosis. Nature Immunology, 21(4), 464-476.

Journal Article Type Article
Acceptance Date Jan 20, 2020
Publication Date Mar 16, 2020
Deposit Date Apr 15, 2020
Publicly Available Date Sep 17, 2020
Journal Nature Immunology
Print ISSN 1529-2908
Publisher Nature Research
Peer Reviewed Peer Reviewed
Volume 21
Issue 4
Pages 464-476
Public URL


12640_Mouse-transcriptome-reveals-potential-signatures-of-protection-and-pathogenesis-in-human-tuberculosis_Accepted.pdf (13.8 Mb)

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