Cording Mycobacterium tuberculosis Bacilli Have a Key Role in the Progression towards Active Tuberculosis, Which is Stopped by Previous Immune Response
Arias, Lilibeth (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Cardona, Paula (Institut Germans Trias i Pujol)
Català, Martí (Centre de Medicina Comparativa i Bioimatge de Catalunya (CMCiB))
Campo Pérez, Víctor (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Prats, Clara (Universitat Politècnica de Catalunya. Escola Superior d'Agricultura de Barcelona)
Vilaplana, Cristina (Institut Germans Trias i Pujol)
Julián Gómez, Esther (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Cardona, Pere-Joan (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)

Data:	2020
Resum:	Cording was the first virulence factor identified in Mycobacterium tuberculosis (Mtb). We aimed to ascertain its role in the induction of active tuberculosis (TB) in the mouse strain C3HeB/FeJ by testing the immunopathogenic capacity of the H37Rv strain. We have obtained two batches of the same strain by stopping their growth in Proskauer Beck liquid medium once the mid-log phase was reached, in the noncording Mtb (NCMtb) batch, and two days later in the cording Mtb (CMtb) batch, when cording could be detected by microscopic analysis. Mice were challenged with each batch intravenously and followed-up for 24 days. CMtb caused a significant increase in the bacillary load at an early stage post-challenge (day 17), when a granulomatous response started, generating exudative lesions characterized by neutrophilic infiltration, which promoted extracellular bacillary growth together with cording formation, as shown for the first time in vivo. In contrast, NCMtb experienced slight or no bacillary growth and lesions could barely be detected. Previous Bacillus Calmette-Guérin (BCG) vaccination or low dose aerosol (LDA) Mtb infection were able to delay the progression towards active TB after CMtb challenge. While BCG vaccination also reduced bacillary load when NCMtb was challenged, LDA did not, and its proliferative lesions experienced neutrophil infiltration. Analysis of lung cytokine and chemokine profiles points to their capacity to block the production of CXCL-1 and further amplification of IL-1β, IL-17 and neutrophilic extracellular trap formation, all of which are essential for TB progression. These data highlight the key role of cording formation in the induction of active TB.
Ajuts:	European Commission 643381 Instituto de Salud Carlos III CPII18/00031 Instituto de Salud Carlos III IFI14/00015 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-500 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-0229
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Mycobacterium tuberculosis ; Cording ; C3HeB/FeJ mice ; Neutrophils ; BCG ; CXCL-1 ; Neutrophilic extracellular traps
Publicat a:	Microorganisms, Vol. 8, Num. 2 (February 2020) , art. 228, ISSN 2076-2607

DOI: 10.3390/microorganisms8020228
PMID: 32046344

14 p, 3.2 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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