English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/209587
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

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

AuthorsSousa, Jeremy; Ca, Baltazar; Maceiras, Ana Raquel; Simoes-Costa, Luisa; Fonseca, Kaori L.; Fernandes, Ana Isabel; Ramos, Angélica; Carvalho, Teresa; Barros, Leandro; Magalhaes, 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; Guimaraes, João Tiago; Bastos, Helder Novais; Osorio, Nuno S.; Comas, Iñaki ; Saraiva, Margarida
Issue Date23-Apr-2020
PublisherNature Publishing Group
CitationNature Communications 11(1):1949 (2020)
AbstractGenetic 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
Description14 páginas, 6 figuras. Supplementary information is available for this paper at https://doi.org/10.1038/s41467-020-15832-6. Sequence data are deposited on NCBI GEO database with the accession code GSE138580
Publisher version (URL)http://dx.doi.org/10.1038/s41467-020-15832-6
URIhttp://hdl.handle.net/10261/209587
DOI10.1038/s41467-020-15832-6
E-ISSN2041-1723
Appears in Collections:(IBV) Artículos
Files in This Item:
File Description SizeFormat 
2020 Nat Commun 11-1949.pdf1,67 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.