title: Deciphering the intracellular fate of Propionibacterium acnes in macrophages.
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.
authors.affiliation: Unit Molecular Microbial Pathogenesis, Pasteur Institute, 75724 Paris, France.
authors.forename: Natalie
authors.initials: N
authors.lastname: Fischer
authors.forename: Tim N
authors.initials: TN
authors.lastname: Mak
authors.forename: Debika Biswal
authors.initials: DB
authors.lastname: Shinohara
authors.forename: Karen S
authors.initials: KS
authors.lastname: Sfanos
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Meyer
authors.forename: Holger
authors.initials: H
authors.lastname: Brüggemann
mesh_terms: D000143:Acids / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002402:Cathepsin D / Q000378:metabolism; D016923:Cell Death; D002460:Cell Line; D011992:Endosomes / Q000378:metabolism; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology / Q000473:pathology; D006801:Humans; D042541:Intracellular Space / Q000382:microbiology*; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000382:microbiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050296:Microbial Viability; D010588:Phagosomes / Q000378:metabolism; D011425:Propionibacterium acnes / Q000254:growth & development / Q000302:isolation & purification / Q000502:physiology*; D011467:Prostate / Q000382:microbiology / Q000473:pathology; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D000143:Acids; D015415:Biomarkers; D002402:Cathepsin D; D051907:Lysosomal Membrane Proteins; D020696:rab5 GTP-Binding Proteins; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1