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

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Sousa, J (Author) Other; Ca, B (Author) Other; Maceiras, AR (Author) Other; Simoes Costa, L (Author) Other; Fonseca, KL (Author) Other; Fernandes, AI (Author) Other; Ramos, A (Author) Other; Carvalho, T (Author) Other; Barros, L (Author) Other; Magalhaes, C (Author) Other; Chiner Oms, A (Author) Other; Machado, H (Author) Other; Veiga, MI (Author) Other; Singh, A (Author) Other; Pereira, R (Author) Other; Amorim, A (Author) FCUP; Vieira, J (Author) ICBAS; Cristina Vieira (Author) ICBAS; Bhatt, A (Author) Other; Rodrigues, F (Author) Other; Rodrigues, P (Author) ICBAS; Gagneux, S (Author) Other; Castro, AG (Author) Other; Guimaraes, JT (Author) Other; Bastos, HN (Author) FMUP; Osorio, NS (Author) Other; Comas, I (Author) Other; Saraiva, M (Author) Other

Journal

Title: Nature Communications

Vol. 11

ISSN: 2041-1723

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 49 Citations

Scopus - 55 Citations

Other information

Authenticus ID: P-00S-1FE

DOI: 10.1038/s41467-020-15832-6

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14