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

Sousa, Jeremy and Cá, Baltazar and Maceiras, Ana Raquel and Simões-Costa, Luisa and Fonseca, Kaori L. and Fernandes, Ana Isabel and Ramos, Angélica and Carvalho, Teresa and Barros, Leandro and Magalhães, Carlos and Chiner-Oms, Álvaro and Machado, Henrique and Veiga, Maria Isabel and Singh, Albel and Pereira, Rui and Amorim, António and Vieira, Jorge and Vieira, Cristina P. and Bhatt, Apoorva and Rodrigues, Fernando and Rodrigues, Pedro N. S. and Gagneux, Sebastien and Castro, António Gil and Guimarães, João Tiago and Bastos, Helder Novais and Osório, Nuno S. and Comas, Iñaki and Saraiva, Margarida. (2020) Mycobacterium tuberculosis associated with severe tuberculosis evades cytosolic surveillance systems and modulates IL-1β production. Nature Communications, 11. p. 1949.

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Official URL: https://edoc.unibas.ch/76489/

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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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Tuberculosis Research (Gagneux)
UniBasel Contributors:Gagneux, Sebastien
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
e-ISSN:2041-1723
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:08 May 2020 06:53
Deposited On:08 May 2020 06:53

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