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Open AccessArticle

Cording Mycobacterium tuberculosis Bacilli Have a Key Role in the Progression towards Active Tuberculosis, Which is Stopped by Previous Immune Response

1
Experimental Tuberculosis Unit (UTE), Fundació Institut d’Investigació en Ciències de la SalutGermans Trias i Pujol (IGTP), 08916 Catalonia, Spain
2
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain
3
Centre de Medicina Comparativa i Bioimatge de Catalunya (CMCiB), 08916 Catalonia, Spain
4
Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, 08193 Catalonia, Spain
5
Bacterial Infections: Antimicrobial Therapies group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), 08028 Catalonia, Spain
6
Departament de Física, Escola Superior d’Agricultura de Barcelona, Universitat Politècnica de Catalunya—BarcelonaTech, 08860 Catalonia, Spain
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Microorganisms 2020, 8(2), 228; https://doi.org/10.3390/microorganisms8020228
Received: 13 December 2019 / Revised: 19 January 2020 / Accepted: 5 February 2020 / Published: 8 February 2020
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. View Full-Text
Keywords: Mycobacterium tuberculosis; cording; C3HeB/FeJ mice; neutrophils; BCG; CXCL-1; neutrophilic extracellular traps Mycobacterium tuberculosis; cording; C3HeB/FeJ mice; neutrophils; BCG; CXCL-1; neutrophilic extracellular traps
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Arias, L.; Cardona, P.; Català, M.; Campo-Pérez, V.; Prats, C.; Vilaplana, C.; Julián, E.; Cardona, P.-J. Cording Mycobacterium tuberculosis Bacilli Have a Key Role in the Progression towards Active Tuberculosis, Which is Stopped by Previous Immune Response. Microorganisms 2020, 8, 228.

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