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Open AccessArticle

A New Model of Chronic Mycobacterium abscessus Lung Infection in Immunocompetent Mice

1
Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
2
Centre of Statistics for Biomedical Sciences (CUSSB), Vita-Salute San Raffaele University, 20132 Milan, Italy
3
Pathology Unit, Department of Experimental Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
4
Preclinical Imaging Facility, Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
5
School of Medicine, Vita-Salute San Raffaele University, 20132 Milan, Italy
6
Infections and Cystic Fibrosis Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(18), 6590; https://doi.org/10.3390/ijms21186590
Received: 30 July 2020 / Revised: 4 September 2020 / Accepted: 7 September 2020 / Published: 9 September 2020
(This article belongs to the Special Issue New Drugs and Novel Strategies against Nontuberculous Mycobacteria)
Pulmonary infections caused by Mycobacterium abscessus (MA) have increased over recent decades, affecting individuals with underlying pathologies such as chronic obstructive pulmonary disease, bronchiectasis and, especially, cystic fibrosis. The lack of a representative and standardized model of chronic infection in mice has limited steps forward in the field of MA pulmonary infection. To overcome this challenge, we refined the method of agar beads to establish MA chronic infection in immunocompetent mice. We evaluated bacterial count, lung pathology and markers of inflammation and we performed longitudinal studies with magnetic resonance imaging (MRI) up to three months after MA infection. In this model, MA was able to establish a persistent lung infection for up to two months and with minimal systemic spread. Lung histopathological analysis revealed granulomatous inflammation around bronchi characterized by the presence of lymphocytes, aggregates of vacuolated histiocytes and a few neutrophils, mimicking the damage observed in humans. Furthermore, MA lung lesions were successfully monitored for the first time by MRI. The availability of this murine model and the introduction of the successfully longitudinal monitoring of the murine lung lesions with MRI pave the way for further investigations on the impact of MA pathogenesis and the efficacy of novel treatments. View Full-Text
Keywords: Mycobacterium abscessus; mouse model; chronic lung infection Mycobacterium abscessus; mouse model; chronic lung infection
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Riva, C.; Tortoli, E.; Cugnata, F.; Sanvito, F.; Esposito, A.; Rossi, M.; Colarieti, A.; Canu, T.; Cigana, C.; Bragonzi, A.; Loré, N.I.; Miotto, P.; Cirillo, D.M. A New Model of Chronic Mycobacterium abscessus Lung Infection in Immunocompetent Mice. Int. J. Mol. Sci. 2020, 21, 6590.

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