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Published on: November 22, 2013
Deciphering the intracellular fate of Propionibacterium acnes in macrophages
Natalie Fischer1, Tim N Mak, Debika Biswal Shinohara
1Unit Molecular Microbial Pathogenesis, Pasteur Institute, 75724 Paris, France.
Abstract:
Propionibacterium acnes is a Gram-positive bacterium that colonizes various niches of the human body, particularly the sebaceous follicles of the skin. Over the last years a role of this common skin bacterium as an opportunistic pathogen has been explored. Persistence of P. acnes in host tissue has been associated with chronic inflammation and disease development, for example, in prostate pathologies. This study investigated the intracellular fate of P. acnes in macrophages after phagocytosis. In a mouse model of P. acnes-induced chronic prostatic inflammation, the bacterium could be detected in prostate-infiltrating macrophages at 2 weeks postinfection. Further studies performed in the human macrophage cell line THP-1 revealed intracellular survival and persistence of P. acnes but no intracellular replication or escape from the host cell. Confocal analyses of phagosome acidification and maturation were performed. Acidification of P. acnes-containing phagosomes was observed at 6 h postinfection but then lost again, indicative of cytosolic escape of P. acnes or intraphagosomal pH neutralization. No colocalization with the lysosomal markers LAMP1 and cathepsin D was observed, implying that the P. acnes-containing phagosome does not fuse with lysosomes. Our findings give first insights into the intracellular fate of P. acnes; its persistency is likely to be important for the development of P. acnes-associated inflammatory diseases.
Insights
Propionibacterium acnes (P. acnes) persists within macrophages, evading lysosomal destruction. This intracellular survival is key to P. acnes-associated chronic inflammation and disease development.
Area of Science:
- Microbiology
- Immunology
- Pathogenesis
Background:
- Propionibacterium acnes (P. acnes) is a skin bacterium increasingly recognized as an opportunistic pathogen.
- P. acnes persistence in host tissues is linked to chronic inflammation and diseases, including prostate pathologies.
Purpose of the Study:
- To investigate the intracellular fate of P. acnes within macrophages following phagocytosis.
- To understand the mechanisms underlying P. acnes persistence in host immune cells.
Main Methods:
- A mouse model of P. acnes-induced chronic prostatic inflammation.
- Studies using the human macrophage cell line THP-1.
- Confocal microscopy to analyze phagosome acidification and maturation, and colocalization with lysosomal markers (LAMP1, cathepsin D).
Main Results:
- P. acnes was detected within prostate-infiltrating macrophages in vivo up to 2 weeks postinfection.
- In vitro, P. acnes survived and persisted within THP-1 macrophages without replicating or escaping.
- Phagosome acidification occurred initially but was subsequently lost, suggesting impaired maturation.
- P. acnes-containing phagosomes did not colocalize with lysosomal markers, indicating a failure of lysosomal fusion.
Conclusions:
- P. acnes exhibits intracellular survival and persistence within macrophages.
- The bacterium evades lysosomal degradation pathways.
- This intracellular persistence is a likely factor in the development of P. acnes-associated inflammatory diseases.
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