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

Jeremy Sousa, Baltazar Cá, Ana Raquel Maceiras, Luisa Simões-Costa, Kaori L. Fonseca, Ana Isabel Fernandes, Angélica Ramos, Teresa Carvalho, Leandro Barros, Carlos Magalhães, Álvaro Chiner-Oms, Henrique Machado, Maria Isabel Veiga, Albel Singh, Rui Pereira, António Amorim, Jorge Vieira, Cristina P. Vieira, Apoorva Bhatt, Fernando Rodrigues, Pedro N. S. Rodrigues, Sebastien Gagneux, António Gil Castro, João Tiago Guimarães, Helder Novais Bastos, Nuno S. Osório, Iñaki Comas and Margarida Saraiva ()
Additional contact information
Jeremy Sousa: University of Porto
Baltazar Cá: University of Porto
Ana Raquel Maceiras: University of Porto
Luisa Simões-Costa: University of Porto
Kaori L. Fonseca: University of Porto
Ana Isabel Fernandes: University of Porto
Angélica Ramos: University of Porto
Teresa Carvalho: University of Porto
Leandro Barros: University of Porto
Carlos Magalhães: University of Minho
Álvaro Chiner-Oms: Biomedicine Institute of Valencia (CSIC)
Henrique Machado: University of Minho
Maria Isabel Veiga: University of Minho
Albel Singh: University of Birmingham
Rui Pereira: University of Porto
António Amorim: University of Porto
Jorge Vieira: University of Porto
Cristina P. Vieira: University of Porto
Apoorva Bhatt: University of Birmingham
Fernando Rodrigues: University of Minho
Pedro N. S. Rodrigues: University of Porto
Sebastien Gagneux: Swiss Tropical and Public Health Institute
António Gil Castro: University of Minho
João Tiago Guimarães: University of Porto
Helder Novais Bastos: University of Porto
Nuno S. Osório: University of Minho
Iñaki Comas: Biomedicine Institute of Valencia (CSIC)
Margarida Saraiva: University of Porto

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15832-6

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DOI: 10.1038/s41467-020-15832-6

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