Mycobacterium tuberculosis associated with severe tuberculosis evades cytosolic surveillance systems and modulates IL-1β production

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Mycobacterium tuberculosis associated with severe tuberculosis evades cytosolic surveillance systems and modulates IL-1β production. / Sousa, Jeremy; Cá, Baltazar; Maceiras, Ana Raquel; Simões-Costa, Luisa; Fonseca, Kaori L; Fernandes, Ana Isabel; Ramos, Angélica; Carvalho, Teresa; Barros, Leandro; Magalhães, Carlos; Chiner-Oms, Álvaro; Machado, Henrique; Veiga, Maria Isabel; Singh, Albel; Pereira, Rui; Amorim, António; Vieira, Jorge; Vieira, Cristina P; Bhatt, Apoorva; Rodrigues, Fernando; Rodrigues, Pedro N S; Gagneux, Sebastien; Castro, António Gil; Guimarães, João Tiago; Bastos, Helder Novais; Osório, Nuno S; Comas, Iñaki; Saraiva, Margarida.

In: Nature Communications, Vol. 11, No. 1, 23.04.2020, p. 1949.

Research output: Contribution to journalArticlepeer-review

Harvard

Sousa, J, Cá, B, Maceiras, AR, Simões-Costa, L, Fonseca, KL, Fernandes, AI, Ramos, A, Carvalho, T, Barros, L, Magalhães, C, Chiner-Oms, Á, Machado, H, Veiga, MI, Singh, A, Pereira, R, Amorim, A, Vieira, J, Vieira, CP, Bhatt, A, Rodrigues, F, Rodrigues, PNS, Gagneux, S, Castro, AG, Guimarães, JT, Bastos, HN, Osório, NS, Comas, I & Saraiva, M 2020, 'Mycobacterium tuberculosis associated with severe tuberculosis evades cytosolic surveillance systems and modulates IL-1β production', Nature Communications, vol. 11, no. 1, pp. 1949. https://doi.org/10.1038/s41467-020-15832-6

APA

Sousa, J., Cá, B., Maceiras, A. R., Simões-Costa, L., Fonseca, K. L., Fernandes, A. I., Ramos, A., Carvalho, T., Barros, L., Magalhães, C., Chiner-Oms, Á., Machado, H., Veiga, M. I., Singh, A., Pereira, R., Amorim, A., Vieira, J., Vieira, C. P., Bhatt, A., ... Saraiva, M. (2020). Mycobacterium tuberculosis associated with severe tuberculosis evades cytosolic surveillance systems and modulates IL-1β production. Nature Communications, 11(1), 1949. https://doi.org/10.1038/s41467-020-15832-6

Vancouver

Author

Sousa, Jeremy ; Cá, Baltazar ; Maceiras, Ana Raquel ; Simões-Costa, Luisa ; Fonseca, Kaori L ; Fernandes, Ana Isabel ; Ramos, Angélica ; Carvalho, Teresa ; Barros, Leandro ; Magalhães, Carlos ; Chiner-Oms, Álvaro ; Machado, Henrique ; Veiga, Maria Isabel ; Singh, Albel ; Pereira, Rui ; Amorim, António ; Vieira, Jorge ; Vieira, Cristina P ; Bhatt, Apoorva ; Rodrigues, Fernando ; Rodrigues, Pedro N S ; Gagneux, Sebastien ; Castro, António Gil ; Guimarães, João Tiago ; Bastos, Helder Novais ; Osório, Nuno S ; Comas, Iñaki ; Saraiva, Margarida. / Mycobacterium tuberculosis associated with severe tuberculosis evades cytosolic surveillance systems and modulates IL-1β production. In: Nature Communications. 2020 ; Vol. 11, No. 1. pp. 1949.

Bibtex

@article{2c64f3fef5354641aaf22276204551a6,
title = "Mycobacterium tuberculosis associated with severe tuberculosis evades cytosolic surveillance systems and modulates IL-1β production",
abstract = "Genetic diversity of Mycobacterium tuberculosis affects immune responses and clinical outcomes of tuberculosis (TB). However, how bacterial diversity orchestrates immune responses to direct distinct TB severities is unknown. Here we study 681 patients with pulmonary TB and show that M. tuberculosis isolates from cases with mild disease consistently induce robust cytokine responses in macrophages across multiple donors. By contrast, bacteria from patients with severe TB do not do so. Secretion of IL-1β is a good surrogate of the differences observed, and thus to classify strains as probable drivers of different TB severities. Furthermore, we demonstrate that M. tuberculosis isolates that induce low levels of IL-1β production can evade macrophage cytosolic surveillance systems, including cGAS and the inflammasome. Isolates exhibiting this evasion strategy carry candidate mutations, generating sigA recognition boxes or affecting components of the ESX-1 secretion system. Therefore, we provide evidence that M. tuberculosis strains manipulate host-pathogen interactions to drive variable TB severities.",
keywords = "Animals, Bacterial Proteins/genetics, Cells, Cultured, Cytokines/metabolism, Cytosol/immunology, Female, Genome, Bacterial/genetics, Humans, Immune Evasion, Immunomodulation, Inflammasomes/immunology, Interleukin-1beta/metabolism, Macrophages/immunology, Male, Mice, Mutation, Mycobacterium tuberculosis/classification, Phylogeny, Polymorphism, Single Nucleotide, Signal Transduction/immunology, Tuberculosis, Pulmonary/immunology, Virulence/genetics",
author = "Jeremy Sousa and Baltazar C{\'a} and Maceiras, {Ana Raquel} and Luisa Sim{\~o}es-Costa and Fonseca, {Kaori L} and Fernandes, {Ana Isabel} and Ang{\'e}lica Ramos and Teresa Carvalho and Leandro Barros and Carlos Magalh{\~a}es and {\'A}lvaro Chiner-Oms and Henrique Machado and Veiga, {Maria Isabel} and Albel Singh and Rui Pereira and Ant{\'o}nio Amorim and Jorge Vieira and Vieira, {Cristina P} and Apoorva Bhatt and Fernando Rodrigues and Rodrigues, {Pedro N S} and Sebastien Gagneux and Castro, {Ant{\'o}nio Gil} and Guimar{\~a}es, {Jo{\~a}o Tiago} and Bastos, {Helder Novais} and Os{\'o}rio, {Nuno S} and I{\~n}aki Comas and Margarida Saraiva",
year = "2020",
month = apr,
day = "23",
doi = "10.1038/s41467-020-15832-6",
language = "English",
volume = "11",
pages = "1949",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Springer",
number = "1",

}

RIS

TY - JOUR

T1 - Mycobacterium tuberculosis associated with severe tuberculosis evades cytosolic surveillance systems and modulates IL-1β production

AU - Sousa, Jeremy

AU - Cá, Baltazar

AU - Maceiras, Ana Raquel

AU - Simões-Costa, Luisa

AU - Fonseca, Kaori L

AU - Fernandes, Ana Isabel

AU - Ramos, Angélica

AU - Carvalho, Teresa

AU - Barros, Leandro

AU - Magalhães, Carlos

AU - Chiner-Oms, Álvaro

AU - Machado, Henrique

AU - Veiga, Maria Isabel

AU - Singh, Albel

AU - Pereira, Rui

AU - Amorim, António

AU - Vieira, Jorge

AU - Vieira, Cristina P

AU - Bhatt, Apoorva

AU - Rodrigues, Fernando

AU - Rodrigues, Pedro N S

AU - Gagneux, Sebastien

AU - Castro, António Gil

AU - Guimarães, João Tiago

AU - Bastos, Helder Novais

AU - Osório, Nuno S

AU - Comas, Iñaki

AU - Saraiva, Margarida

PY - 2020/4/23

Y1 - 2020/4/23

N2 - Genetic diversity of Mycobacterium tuberculosis affects immune responses and clinical outcomes of tuberculosis (TB). However, how bacterial diversity orchestrates immune responses to direct distinct TB severities is unknown. Here we study 681 patients with pulmonary TB and show that M. tuberculosis isolates from cases with mild disease consistently induce robust cytokine responses in macrophages across multiple donors. By contrast, bacteria from patients with severe TB do not do so. Secretion of IL-1β is a good surrogate of the differences observed, and thus to classify strains as probable drivers of different TB severities. Furthermore, we demonstrate that M. tuberculosis isolates that induce low levels of IL-1β production can evade macrophage cytosolic surveillance systems, including cGAS and the inflammasome. Isolates exhibiting this evasion strategy carry candidate mutations, generating sigA recognition boxes or affecting components of the ESX-1 secretion system. Therefore, we provide evidence that M. tuberculosis strains manipulate host-pathogen interactions to drive variable TB severities.

AB - Genetic diversity of Mycobacterium tuberculosis affects immune responses and clinical outcomes of tuberculosis (TB). However, how bacterial diversity orchestrates immune responses to direct distinct TB severities is unknown. Here we study 681 patients with pulmonary TB and show that M. tuberculosis isolates from cases with mild disease consistently induce robust cytokine responses in macrophages across multiple donors. By contrast, bacteria from patients with severe TB do not do so. Secretion of IL-1β is a good surrogate of the differences observed, and thus to classify strains as probable drivers of different TB severities. Furthermore, we demonstrate that M. tuberculosis isolates that induce low levels of IL-1β production can evade macrophage cytosolic surveillance systems, including cGAS and the inflammasome. Isolates exhibiting this evasion strategy carry candidate mutations, generating sigA recognition boxes or affecting components of the ESX-1 secretion system. Therefore, we provide evidence that M. tuberculosis strains manipulate host-pathogen interactions to drive variable TB severities.

KW - Animals

KW - Bacterial Proteins/genetics

KW - Cells, Cultured

KW - Cytokines/metabolism

KW - Cytosol/immunology

KW - Female

KW - Genome, Bacterial/genetics

KW - Humans

KW - Immune Evasion

KW - Immunomodulation

KW - Inflammasomes/immunology

KW - Interleukin-1beta/metabolism

KW - Macrophages/immunology

KW - Male

KW - Mice

KW - Mutation

KW - Mycobacterium tuberculosis/classification

KW - Phylogeny

KW - Polymorphism, Single Nucleotide

KW - Signal Transduction/immunology

KW - Tuberculosis, Pulmonary/immunology

KW - Virulence/genetics

U2 - 10.1038/s41467-020-15832-6

DO - 10.1038/s41467-020-15832-6

M3 - Article

C2 - 32327653

VL - 11

SP - 1949

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

ER -