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Mouse models to study host-pathogens interaction in Mycobacterium abscessus lung infections.

F Saliu(1) N Francesca(1) D Cirillo(1) N Lorè(1)

1:San Raffaele Scientific Institute

Mycobacterium abscessus is a non-tuberculous mycobacterium (NTM) able to cause progressive pulmonary infections, named NTM pulmonary disease. The therapeutic approaches are limited, and infections are difficult to treat due to antibiotic resistance conferred by an impermeable cell wall, drug efflux pumps, or drug-modifying enzymes. The development of new therapeutics, intended as antimicrobials or drug limiting immunopathology, is urgently necessary. We recently set up a preclinical murine models of M. abscessus representing an useful tool to validate and translate in vitro-proofed concepts. In addition to acute model of lung infection, we refined an agar beads mouse model to establish M. abscessus chronic infection in the airway of immunocompetent mice. In this model, M. abscessus is able to establish a persistent lung infection for more than one month with a stable bacterial load. Thanks to these models, it is possible to monitor both pulmonary mycobacterial burdens and inflammatory responses occurring during the development of acute or chronic respiratory infection. The exploitation of this model is allowing us to prove its relevance for the identification of novel therapeutic targets fighting M. abscessus infection and its immunopathological consequence. In conclusion, the developed and characterized murine models are useful for future mechanistic studies in the field of M. abscessus-host interaction.

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