Mycobacterium tuberculosis associated with severe tuberculosis evades cytosolic surveillance systems and modulates IL-1 beta production
Por:
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 and Saraiva M
Publicada:
23 abr 2020
Ahead of Print:
23 abr 2020
Resumen:
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-1 beta 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-1 beta 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. Some strains of Mycobacterium tuberculosis seem to be able to avoid host defense systems. Here the authors stratify patients by severity of tuberculosis and find correlations with the level of IL-1 beta production by macrophages exposed to these isolates.
Filiaciones:
Sousa J:
i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
IBMC-Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal
Doctoral Program in Molecular and Cell Biology, ICBAS-Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal
Cá B:
i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
IBMC-Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal
Doctoral Program in Molecular and Cell Biology, ICBAS-Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal
Maceiras AR:
i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
IBMC-Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal
Simões-Costa L:
i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
IBMC-Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal
Fonseca KL:
i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
IBMC-Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal
Doctoral Program in Molecular and Cell Biology, ICBAS-Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal
Fernandes AI:
i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
IBMC-Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal
Ramos A:
São João Hospital Center & EPIUnit-Institute of Public Health, University of Porto, Porto, Portugal
Carvalho T:
São João Hospital Center & EPIUnit-Institute of Public Health, University of Porto, Porto, Portugal
Barros L:
i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
IBMC-Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal
Magalhães C:
Life and Health Sciences Research Institute, University of Minho, Braga, Portugal
ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
:
Biomedicine Institute of Valencia (CSIC), Valencia, Spain
Machado H:
Life and Health Sciences Research Institute, University of Minho, Braga, Portugal
ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
Veiga MI:
Life and Health Sciences Research Institute, University of Minho, Braga, Portugal
ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
Singh A:
School of Biosciences and Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK
Pereira R:
i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
IPATIMUP-Institute of Molecular Pathology and Immunology of the University of Porto, University of Porto, Porto, Portugal
Amorim A:
i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
IPATIMUP-Institute of Molecular Pathology and Immunology of the University of Porto, University of Porto, Porto, Portugal
Faculty of Sciences, University of Porto, Porto, Portugal
Vieira J:
i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
IBMC-Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal
Vieira CP:
i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
IBMC-Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal
Bhatt A:
School of Biosciences and Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK
Rodrigues F:
Life and Health Sciences Research Institute, University of Minho, Braga, Portugal
ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
Rodrigues PNS:
i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
IBMC-Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal
ICBAS-Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal
Gagneux S:
Swiss Tropical and Public Health Institute, Basel, Switzerland
University of Basel, Basel, Switzerland
Castro AG:
Life and Health Sciences Research Institute, University of Minho, Braga, Portugal
ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
Guimarães JT:
São João Hospital Center & EPIUnit-Institute of Public Health, University of Porto, Porto, Portugal
Faculty of Medicine, University of Porto, Porto, Portugal
Bastos HN:
i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
IBMC-Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal
Faculty of Medicine, University of Porto, Porto, Portugal
São João Hospital Center, Porto, Portugal
Osório NS:
Life and Health Sciences Research Institute, University of Minho, Braga, Portugal
ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
:
Biomedicine Institute of Valencia (CSIC), Valencia, Spain
CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain
Saraiva M:
i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal.
IBMC-Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal.
Green Published, Green Accepted, gold
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