Repetitive Aerosol Exposure Promotes Cavitary Tuberculosis and Enables Screening for Targeted Inhibitors of Extensive Lung Destruction.
J Infect Dis
; 218(1): 53-63, 2018 06 05.
Article
em En
| MEDLINE
| ID: mdl-29554286
ABSTRACT
Background:
Cavitation is a serious consequence of tuberculosis. We tested the hypothesis that repetitive exposure to the same total bacterial burden of Mycobacterium tuberculosis drives greater lung destruction than a single exposure. We also tested whether inhibition of endogenous matrix metalloproteinase-1 (MMP-1) may inhibit cavitation during tuberculosis.Methods:
Over a 3-week interval, we infected rabbits with either 5 aerosols of 500 colony-forming units (CFU) of M. tuberculosis or a single aerosol of 2500 CFU plus 4 sham aerosols. We administered the MMP-1 inhibitor cipemastat (100 mg/kg daily) during weeks 5-10 to a subset of the animals.Results:
Repetitive aerosol infection produced greater lung inflammation and more cavities than a single aerosol infection of the same bacterial burden (75% of animals vs 25%). Necropsies confirmed greater lung pathology in repetitively exposed animals. For cipemastat-treated animals, there was no significant difference in cavity counts, cavity volume, or disease severity compared to controls.Conclusions:
Our data show that repetitive aerosol exposure with M. tuberculosis drives greater lung damage and cavitation than a single exposure. This suggests that human lung destruction due to tuberculosis may be exacerbated in settings where individuals are repeatedly exposed. MMP-1 inhibition with cipemastat did not prevent the development of cavitation in our model.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tuberculose Pulmonar
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Aerossóis
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Metaloproteinase 1 da Matriz
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Exposição Ambiental
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Pulmão
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Mycobacterium tuberculosis
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article