Unravelling the transcriptome of the human tuberculosis lesion and its clinical implications
Por:
Fonseca, KL, Lozano, JJ, Despuig, A, Habgood-Coote, D, Sidorova, J, Aznar, D, Arias, L, del Río-Alvarez, A, Carrillo-Reixach, J, Goff, A, Wildner, LM, Gogishvili, S, Nikolaishvili, K, Shubladze, N, Avaliani, Z, Tapia, G, Rodríguez-Martínez, P, Cardona, PJ, Martinón-Torres, F, Salas, A, Gómez-Carballa, A, Armengol, C, Waddell, SJ, Kaforou, M, O'Garra, A, Vashakidze, S and Vilaplana, C
Publicada:
30 may 2025
Ahead of Print:
30 may 2025
Resumen:
The tuberculosis (TB) lesion is a complex structure, contributing to the overall spectrum of TB. We characterise, using RNA sequencing, 44 fresh human pulmonary TB lesion samples from 13 TB individuals (drug-sensitive and multidrug-resistant TB) undergoing therapeutic surgery. We confirm clear separation between the TB lesion and adjacent non-lesional tissue, with the lesion samples consistently displaying increased inflammatory profile despite heterogeneity. Using weighted correlation network analysis, we identify 17 transcriptional modules associated with TB lesion and demonstrate a gradient of immune-related transcript abundance according to spatial organization of the lesion. Furthermore, we associate the modular transcriptional signature of the TB lesion with clinical surrogates of treatment efficacy and TB severity. We show that patients with worse disease present an overabundance of immune/inflammation-related modules and downregulated tissue repair and metabolism modules. Our findings provide evidence of a relationship between clinical parameters, treatment response and immune signatures at the infection site.
Filiaciones:
:
Fundacio Inst Germans Trias & Pujol IGTP, Expt TB Unit UTE, Badalona, Spain
Ctr Invest Biomed Red Enfermedades Resp CIBERES, Madrid, Spain
Lozano, JJ:
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Bioinformat Platform, Barcelona, Spain
Hosp Clin Barcelona, Barcelona, Spain
Despuig, A:
Fundacio Inst Germans Trias & Pujol IGTP, Expt TB Unit UTE, Badalona, Spain
Ctr Invest Biomed Red Enfermedades Resp CIBERES, Madrid, Spain
Habgood-Coote, D:
Imperial Coll London, Dept Infect Dis, London, England
Sidorova, J:
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Bioinformat Platform, Barcelona, Spain
Hosp Clin Barcelona, Barcelona, Spain
Aznar, D:
Fundacio Inst Germans Trias & Pujol IGTP, Expt TB Unit UTE, Badalona, Spain
Univ Autonoma Barcelona UAB, Dept Genet & Microbiol, Bellaterra, Spain
:
Fundacio Inst Germans Trias & Pujol IGTP, Expt TB Unit UTE, Badalona, Spain
Ctr Invest Biomed Red Enfermedades Resp CIBERES, Madrid, Spain
del Río-Alvarez, A:
Germans Trias & Pujol Res Inst IGTP, Childhood Liver Oncol Grp, Badalona, Spain
Germans Trias & Pujol Res Inst IGTP, Translat Program Canc Res CARE, Badalona, Spain
Liver & Digest Dis Networking Biomed Res Ctr CIBER, Madrid, Spain
Carrillo-Reixach, J:
Germans Trias & Pujol Res Inst IGTP, Childhood Liver Oncol Grp, Badalona, Spain
Germans Trias & Pujol Res Inst IGTP, Translat Program Canc Res CARE, Badalona, Spain
Liver & Digest Dis Networking Biomed Res Ctr CIBER, Madrid, Spain
Goff, A:
Univ Sussex, Brighton & Sussex Med Sch, Global Hlth & Infect, Brighton, England
Wildner, LM:
Univ Sussex, Brighton & Sussex Med Sch, Global Hlth & Infect, Brighton, England
Gogishvili, S:
Natl Ctr TB & Lung Dis NCTLD, Tbilisi, Georgia
Nikolaishvili, K:
Natl Ctr TB & Lung Dis NCTLD, Tbilisi, Georgia
Shubladze, N:
Natl Ctr TB & Lung Dis NCTLD, Tbilisi, Georgia
Avaliani, Z:
Natl Ctr TB & Lung Dis NCTLD, Tbilisi, Georgia
European Univ, Tbilisi, Georgia
:
Hosp Badalona Germans Trias & Pujol, Pathol Dept, Badalona, Spain
Univ Autonoma Barcelona, Barcelona, Spain
Rodríguez-Martínez, P:
Hosp Badalona Germans Trias & Pujol, Pathol Dept, Badalona, Spain
Univ Autonoma Barcelona, Barcelona, Spain
:
Fundacio Inst Germans Trias & Pujol IGTP, Expt TB Unit UTE, Badalona, Spain
Ctr Invest Biomed Red Enfermedades Resp CIBERES, Madrid, Spain
Univ Autonoma Barcelona UAB, Dept Genet & Microbiol, Bellaterra, Spain
Hosp Badalona Germans Trias & Pujol, Microbiol Dept, Northern Metropolitan Clin Lab, Badalona, Spain
Martinón-Torres, F:
Ctr Invest Biomed Red Enfermedades Resp CIBERES, Madrid, Spain
Inst Invest Sanitaria Santiago IDIS, Genet Vaccines & Pediat Infect Dis Res Grp GENVIP, Santiago De Compostela, Spain
Univ Santiago De Compostela USC, Santiago De Compostela, Spain
Hosp Clin Univ Santiago De Compostela SERGAS, Translat Pediat & Infect Dis, Santiago De Compostela, Spain
Salas, A:
Ctr Invest Biomed Red Enfermedades Resp CIBERES, Madrid, Spain
Hosp Clin Univ Santiago De Compostela SERGAS, Translat Pediat & Infect Dis, Santiago De Compostela, Spain
Univ Santiago De Compostela, Unidade Xenet, Inst Ciencias Forenses INCIFOR, Santiago De Compostela, Spain
Inst Invest Sanitaria IDIS, GenPoB Res Grp, Santiago De Compostela, Spain
Gómez-Carballa, A:
Ctr Invest Biomed Red Enfermedades Resp CIBERES, Madrid, Spain
Hosp Clin Univ Santiago De Compostela SERGAS, Translat Pediat & Infect Dis, Santiago De Compostela, Spain
Univ Santiago De Compostela, Unidade Xenet, Inst Ciencias Forenses INCIFOR, Santiago De Compostela, Spain
Inst Invest Sanitaria IDIS, GenPoB Res Grp, Santiago De Compostela, Spain
:
Germans Trias & Pujol Res Inst IGTP, Childhood Liver Oncol Grp, Badalona, Spain
Germans Trias & Pujol Res Inst IGTP, Translat Program Canc Res CARE, Badalona, Spain
Liver & Digest Dis Networking Biomed Res Ctr CIBER, Madrid, Spain
Waddell, SJ:
Univ Sussex, Brighton & Sussex Med Sch, Global Hlth & Infect, Brighton, England
Kaforou, M:
Imperial Coll London, Dept Infect Dis, London, England
Imperial Coll London, Ctr Paediat & Child Hlth, London, England
O'Garra, A:
Francis Crick Inst, Immunoregulat & Infect Lab, London, England
Imperial Coll, Natl Heart & Lung Inst, London, England
Vashakidze, S:
Natl Ctr TB & Lung Dis NCTLD, Tbilisi, Georgia
Univ Georgia, Tbilisi, Georgia
:
Fundacio Inst Germans Trias & Pujol IGTP, Expt TB Unit UTE, Badalona, Spain
Ctr Invest Biomed Red Enfermedades Resp CIBERES, Madrid, Spain
Univ Autonoma Barcelona UAB, Dept Genet & Microbiol, Bellaterra, Spain
Hosp Badalona Germans Trias & Pujol, Microbiol Dept, Northern Metropolitan Clin Lab, Badalona, Spain
Green Submitted, gold
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