Development and multimodal characterization of an elastase-induced emphysema mouse disease model for the COPD frequent bacterial exacerbator phenotype
| Autor: | Begoña Euba, Irene Rodríguez-Arce, Derek W. Hood, Mikel Ariz, Xabier Morales, Maider Esparza, Junkal Garmendia, Nahikari López-López, José Leiva, Carlos Ortiz-de-Solorzano |
|---|---|
| Přispěvatelé: | Diputación Foral de Navarra, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Ministerio de Economía y Competitividad (España), Sociedad Española de Neumología y Cirugía Torácica |
| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
Micro-CT Haemophilus Infections Bacterial exacerbation Test of pulmonary function Immunology Pulmonary disease Inflammation Lung emphysema Disease Infectious and parasitic diseases RC109-216 Biology Microbiology Mice Pulmonary Disease Chronic Obstructive medicine Animals Humans Micro ct COPD Pancreatic Elastase Elastase medicine.disease Phenotype Haemophilus influenzae Disease Models Animal Infectious Diseases Pulmonary Emphysema Disease Progression Parasitology medicine.symptom Research Article Research Paper |
| Zdroj: | Virulence, Vol 12, Iss 1, Pp 1672-1688 (2021) Virulence article-version (VoR) Version of Record Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 2150-5608 2150-5594 |
| Popis: | Chronic obstructive pulmonary disease (COPD) patients undergo infectious exacerbations whose frequency identifies a clinically meaningful phenotype. Mouse models have been mostly used to separately study both COPD and the infectious processes, but a reliable model of the COPD frequent exacerbator phenotype is still lacking. Accordingly, we first established a model of single bacterial exacerbation by nontypeable Haemophilus influenzae (NTHi) infection on mice with emphysema-like lesions. We characterized this single exacerbation model combining both noninvasive in vivo imaging and ex vivo techniques, obtaining longitudinal information about bacterial load and the extent of the developing lesions and host responses. Bacterial load disappeared 48 hours post-infection (hpi). However, lung recovery, measured using tests of pulmonary function and the disappearance of lung inflammation as revealed by micro-computed X-ray tomography, was delayed until 3 weeks post-infection (wpi). Then, to emulate the frequent exacerbator phenotype, we performed two recurrent episodes of NTHi infection on the emphysematous murine lung. Consistent with the amplified infectious insult, bacterial load reduction was now observed 96 hpi, and lung function recovery and disappearance of lesions on anatomical lung images did not happen until 12 wpi. Finally, as a proof of principle of the use of the model, we showed that azithromycin successfully cleared the recurrent infection, confirming this macrolide utility to ameliorate infectious exacerbation. In conclusion, we present a mouse model of recurrent bacterial infection of the emphysematous lung, aimed to facilitate investigating the COPD frequent exacerbator phenotype by providing complementary, dynamic information of both infectious and inflammatory processes. This work was supported by the Departamento de Universidad, Innovación y Transformación Digital, Gobierno de Navarra [PC150-151-152]; Ministerio de Ciencia, Innovación y Universidades (MICIU), Gobierno de España [RTI2018-096369-B-I00]; MICIU, Gobierno de España [RED2018-102469-T]; MICIU , Gobierno de España [SAF2015-66520-R]; MICIU , Gobierno de España [RTI2018- 094494-B-C222]; Departamento de Salud, Gobierno de Navarra [03/2016]; Sociedad Española de Neumología y Cirugía Torácica [31/2015]. |
| Databáze: | OpenAIRE |
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