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Mycobacterium tuberculosis associated with severe tuberculosis evades cytosolic surveillance systems to modulate IL-1β production

AuthorsSousa, J.; Ca, B.; Maceiras, A.; Fonseca, K.; Costa, A.; Fernandes, A.; Ramos, A.; Carvalho, T.; Barros, L.; Magalhães, C.; Machado, H.; Veiga, M. I.; Pereira, R.; Amorim, A.; Vieira, J.; Vieira, C.; Bhatt, A.; Rodrigues, F.; Rodrigues, P.; Gagneux, S.; Comas, Iñaki ; Castro, A. G.; Osório, N. S.; Guimarães, J. T.; Bastos, H. N.; Saraiva, M.
Issue Date19-Sep-2019
CitationScientific Meeting on Mycobacteria. MycoPORTO 2019 Porto (Portugal)
AbstractTuberculosis (TB) remains a major health concern worldwide, causing over one million deaths per year and latent infection in about one-fourth of the world population. The variability of the disease outcomes is one of the most striking features of TB, being classically related to host factors. However, recent evidence place the genetic variability within the bacteria strains as an important determinant of clinical outcomes of TB. Through a retrospective study of over 800 TB cases combined with the phylogenetic structure of the infecting bacteria and of its interaction with human immune cells, we found that Mycobacterium tuberculosis isolated from patients with more severe forms of TB are generally poor triggers of the host immune response. By combining RNA-Seq and functional analysis, we relate this poor induction of cytokine production with a differential capacity of the different clinical isolates in activating cytosolic surveillance systems, including cGAS and the NLRP3 inflammasome. This in turn impacts type I IFN and IL-1β production by infected immune cells. At the bacterial level, we found an accumulation of mutations in the ESX secretion system components related to this evasion strategy. Our studies are for the first time establishing clear bacterial genotype-immune phenotype-clinical links, offering host immune pathways and bacterial signatures to be targeted in the design of novel TB interventions.
DescriptionAbstract de póster presentado al Scientific Meeting on Mycobacteria. MycoPORTO 2019 Porto (Portugal), 19-20 de septiembre de 2019
Appears in Collections:(IBV) Comunicaciones congresos
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