FFC#20/2017

Establishment of animal model to investigate pathogenesis of infection by Mycobacterium abscessus complex members in cystic fibrosis patients

FFC#20/2017

Establishment of animal model to investigate pathogenesis of infection by Mycobacterium abscessus complex members in cystic fibrosis patients

PRINCIPAL INVESTIGATOR

Enrico Tortoli (Unità Batteri Patogeni Emergenti, Divisione di Immunologia, Trapianti e Malattie Infettive, Istituto San Raffaele, Milano)

Partner

Carla Colombo (Fondazione IRCSS Ca’ Granda, Ospedale Maggiore Policlinico, Milano); Mariaclelia Di Serio (CUSSB, Centro Universitario di Statistica per le Scienze Biomediche, Università San Raffaele, Milano)

RESEARCHERS

8

CATEGORY

AREA 3 Bronchopulmonary infection

DURATION

1 year

GOAL

€ 55.000 €

RESULTS

The hypothesis is that strains of Mycobacterium abscessus (M.a.) isolated from patients with deteriorated lung functionality may differ in pathogenicity from the ones isolated from asymptomatic patients. For this reason, researchers investigated the pathogenicity of the M.a. subspecies (subs) in mice models to discover different biological evidence of pulmonary infection, in order to discriminate between severe pathogen M.a. subs forms. M.a. subs reference strains (M.a. abscessus, M.a. bolletii and M.a. massiliense) and isolate from CF patients were used to establish a chronic infection in WT and CF mice up to six months. Pulmonary mice lesions were monitored by magnetic resonance imaging (MRI) and at different time points, mice lungs were processed for microbiological analysis, inflammatory response and histological evaluation. Researchers were able to establish a long-term (up to 3months) chronic lung infection in WT and CF mice with a stable bacterial load. This event was never obtained before. After 6 months of M.a. infection the lung was still characterized by a granulomatous response; the persistence of the lung infectious foci was confirmed with MRI and cytokines/chemokines level dosage. Some animal cleared M.a. infection, others did not. The availability of this murine model and the longitudinal MRI monitoring of mice will hopefully allow identifying the M.a. isolates responsible for severe disease and to investigate in vivo the impact of novel therapeutic protocols.


 Congress abstracts

– Riva C, Gona F, Cigana C et al. “Murine model of chronic M. abscessus respiratory infection” North American Cystic Fibrosis Conference (NACF), November 2-4, 2017, Indianapolis, IN, USA
– Riva C, Gona F, Cigana C et al. “Characterization of murine model of chronic M. abscessus respiratory infection” ERS International Congress, September 16-18, Paris, France

OTHER RESULTS

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