期刊
VIRULENCE
卷 8, 期 8, 页码 1761-1775出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/21505594.2017.1361089
关键词
invasion; macrophage; persistence; phagocytosis; Staphylococcus aureus
资金
- Plan Nacional de I+D +I [PI13/01418]
- ISCIII- Subdireccion General de Evaluacion
- Fondo Europeo de Desarrollo Regional (FEDER)
- Spanish Society of Pneumology and Thoracic Surgery [SEPAR 054/2011]
- Instituto de Salud Carlos III: CIBERES (Corporate Research Program on Host-Pathogen interactions)
- Plan Nacional de I+D +I
- joint ERS/SEPAR fellowship (LTRF)
- Sociedad Espanola de Microbiologia Clinica y Enfermedades Infecciosas (SEIMC)
- CIBERES (Programa de perfeccionamiento y movilidad)
Objective: Staphylococcus aureus is a particularly difficult pathogen to eradicate from the respiratory tract. Previous studies have highlighted the intracellular capacity of S. aureus in several phagocytic and non-phagocytic cells. The aim of this study was to define S. aureus interaction within a murine alveolar macrophage cell line. Methods: Cell line MH-S was infected with Newman strain. Molecular mechanisms involved in phagocytosis were explored. To assess whether S. aureus survives intracellularly quantitative (gentamicin protection assays and bacterial plating) and qualitative analysis (immunofluorescence microscopy) were performed. Bacterial colocalization with different markers of the endocytic pathway was examined to characterize its intracellular trafficking. Results: We found that S. aureus uptake requires host actin polymerization, microtubule assembly and activation of phosphatidylinositol 3-kinase signaling. Time course experiments showed that Newman strain was able to persist within macrophages at least until 28.5 h post infection. We observed that intracellular bacteria are located inside an acidic subcellular compartment, which co-localizes with the late endosome/lysosome markers Lamp-1, Rab7 and RILP. Colocalization counts with TMR-dextran might reflect a balance between bacterial killing and intracellular survival. Conclusions: This study indicates that S. aureus persists and replicates inside murine alveolar macrophages, representing a privileged niche that can potentially offer protection from antimicrobial activity and immunological host defense mechanisms.
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