Unravelling the transcriptome of the human tuberculosis lesion and its clinical implications

Autor: Albert Despuig, Kaori L. Fonseca, Dominic Habgood-Coote, Álvaro Del Río-Álvarez, Juan Carrillo-Reixach, Lilibeth Arias, Nino Gogichadze, Aaron Goff, Leticia Muraro Wildner, Shota Gogishvili, Keti Nikolaishvili, Natalia Shubladze, Zaza Avaliani, Pere-Joan Cardona, Federico Martinón-Torres, Antonio Salas, Alberto Gómez-Carballa, Simon J Waddell, Carolina Armengol, Sergo Vashakidze, Myrsini Kaforou, Cristina Vilaplana
Rok vydání: 2022
Popis: Tuberculosis (TB) disease causes up to 1.5 million deaths every year and represents an important problem of public health at worldwide level. Here, we quantified the gene expression signatures of granuloma biopsies across human TB pulmonary lesions, and validated the best gene candidates using NanoString technology, profiling 157 samples from 40 TB patients who underwent surgery.We characterised the transcriptional profile of the TB granuloma in comparison to healthy tissue, described an 11-gene signature and measured 7 proteins in plasma associated with it. We demonstrated a gradient of immune-related transcript abundance across the granuloma substructure and evidenced metabolically-activeMycobacterium tuberculosisin the lesions. Patients who converted to sputum negative after two months of starting treatment, showed enriched inflammatory pathways in the lesion several months after, supporting use of sputum culture conversion (SCC) as a prognostic biomarker during clinical management and as a factor to prioritise patients when considering lung surgery.
Databáze: OpenAIRE