Abstract
Mycobacterium abscessus represents an important respiratory pathogen among the rapidly-growing non-tuberculous mycobacteria. Infections caused by M. abscessus are increasingly found in cystic fibrosis (CF) patients and are often refractory to antibiotic therapy. The underlying immunopathological mechanisms of pathogenesis remain largely unknown. A major reason for the poor advances in M. abscessus research has been a lack of adequate models to study the acute and chronic stages of the disease leading to delayed progress of evaluation of therapeutic efficacy of potentially active antibiotics. However, the recent development of cellular models led to new insights in the interplay between M. abscessus with host macrophages as well as with amoebae, proposed to represent the environmental host and reservoir for non-tuberculous mycobacteria. The zebrafish embryo has also appeared as a useful alternative to more traditional models as it recapitulates the vertebrate immune system and, due to its optical transparency, allows a spatio-temporal visualization of the infection process in a living animal. More sophisticated immunocompromised mice have also been exploited recently to dissect the immune and inflammatory responses to M. abscessus. Herein, we will discuss the limitations, advantages and potential offered by these various models to study the pathophysiology of M. abscessus infection and to assess the preclinical efficacy of compounds active against this emerging human pathogen.
Highlights
Epidemiological studies indicate that the presence of R variants are associated with the most severe cases of pulmonary infections which can persist for years (Jönsson et al, 2007; Catherinot et al, 2009)
Our knowledge of the pathophysiological characteristics and mechanisms governing virulence of the R or S variants has long been obscured by the lack of animal models that are permissive to Mycobacterium abscessus (Mabs) infection
IFN-γ knockout (GKO) mice infected with a LDA or HDA of Mabs resulted in a low amount of persistent Mabs lung infection inducing influx of T cells, macrophages and dendritic cells, which contributed to granuloma formation
Summary
Mycobacterium abscessus (Mabs) is a rapidly-growing mycobacterial species, regarded as an important pathogen responsible for a wide array of clinical manifestations in humans, ranging from cutaneous infections to severe chronic pulmonary infections, usually encountered in immunocompromised and in cystic fibrosis (CF) patients (Griffith et al, 1993; Olivier et al, 2003; Jönsson et al, 2007; Roux et al, 2009; Leão et al, 2010; Qvist et al, 2015; Bryant et al, 2016). Infection of classical immunocompetent mouse models leads to transient colonization, impeding their use as a valuable animal models to study chronic disease and the in vivo therapeutic efficacy of drugs (Bernut et al, 2014b).
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