Colony-stimulating factor-1- and interleukin-34-derived macrophages differ in their susceptibility to Mycobacterium marinum.
J Leukoc Biol
; 106(6): 1257-1269, 2019 12.
Article
en En
| MEDLINE
| ID: mdl-31535730
ABSTRACT
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains the leading global cause of death from an infectious agent. Mycobacteria thrive within their host MÏs and presently, there is no animal model that permits combined in vitro and in vivo study of mycobacteria-host MÏ interactions. Mycobacterium marinum (Mm), which causes TB in aquatic vertebrates, has become a promising model for TB research, owing to its close genetic relatedness to Mtb and the availability of alternative, natural host aquatic animal models. Here, we adopted the Xenopus laevis frog-Mm surrogate infection model to study host MÏ susceptibility and resistance to mycobacteria. MÏ differentiation is regulated though the CSF-1 receptor (CSF-1R), which is activated by CSF-1 and the unrelated IL-34 cytokines. Using combined in vitro and in vivo approaches, we demonstrated that CSF-1-MÏs exacerbate Mm infections, are more susceptible to mycobacterial entry and are less effective at killing this pathogen. By contrast, IL-34-MÏs confer anti-Mm resistance in vivo, are less susceptible to Mm entry and more effectively eliminate internalized mycobacteria. Moreover, we showed that the human CSF-1- and IL-34-MÏs are likewise, respectively, susceptible and resistant to mycobacteria, and that both frog and human CSF-1-MÏs are more prone to the spread of mycobacteria and to being infected by Mm-laden MÏs than the respective IL-34-MÏ subsets. This work marks the first report describing the roles of these MÏ subsets in mycobacterial disease and may well lead to the development of more targeted anti-Mtb approaches.
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Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Factor Estimulante de Colonias de Macrófagos
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Interleucinas
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Mycobacterium marinum
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Macrófagos
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Infecciones por Mycobacterium no Tuberculosas
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Leukoc Biol
Año:
2019
Tipo del documento:
Article