title: TLR-2 Recognizes Propionibacterium acnes CAMP Factor 1 from Highly Inflammatory Strains.
abstract: BACKGROUND
  Propionibacterium acnes (P. acnes) is an anaerobic, Gram-positive bacteria encountered in inflammatory acne lesions, particularly in the pilosebaceous follicle. P. acnes triggers a strong immune response involving keratinocytes, sebocytes and monocytes, the target cells during acne development. Lipoteicoic acid and peptidoglycan induce the inflammatory reaction, but no P. acnes surface protein interacting with Toll-like receptors has been identified. P. acnes surface proteins have been extracted by lithium stripping and shown to induce CXCL8 production by keratinocytes.
  
  
  RESULTS
  Far-western blotting identified two surface proteins, of 24.5- and 27.5-kDa in size, specifically recognized by TLR2. These proteins were characterized, by LC-MS/MS, as CAMP factor 1 devoid of its signal peptide sequence, as shown by N-terminal sequencing. Purified CAMP factor 1 induces CXCL8 production by activating the CXCL8 gene promoter, triggering the synthesis of CXCL8 mRNA. Antibodies against TLR2 significantly decreased the CXCL8 response. For the 27 P. acnes strains used in this study, CAMP1-TLR2 binding intensity was modulated and appeared to be strong in type IB and II strains, which produced large amounts of CXCL8, whereas most of the type IA1 and IA2 strains presented little or no CAMP1-TLR2 binding and low levels of CXCL8 production. The nucleotide sequence of CAMP factor displays a major polymorphism, defining two distinct genetic groups corresponding to CAMP factor 1 with 14 amino-acid changes from strains phylotyped II with moderate and high levels of CAMP1-TLR2 binding activity, and CAMP factor 1 containing 0, 1 or 2 amino-acid changes from strains phylotyped IA1, IA2, or IB presenting no, weak or moderate CAMP1-TLR2 binding.
  
  
  CONCLUSIONS
  Our findings indicate that CAMP factor 1 may contribute to P. acnes virulence, by amplifying the inflammation reaction through direct interaction with TLR2.
authors.affiliation: Université Sorbonne Paris Descartes, Faculté de Médecine, INSERM, Institut Cochin, Laboratoire de Dermatologie-CNR Syphilis, Paris, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Lheure
authors.affiliation: Université Sorbonne Paris Descartes, Faculté de Médecine, INSERM, Institut Cochin, Laboratoire de Dermatologie-CNR Syphilis, Paris, France.
authors.forename: Philippe Alain
authors.initials: PA
authors.lastname: Grange
authors.affiliation: Université Sorbonne Paris Descartes, Faculté de Médecine, INSERM, Institut Cochin, Laboratoire de Dermatologie-CNR Syphilis, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Ollagnier
authors.affiliation: AP-HP, Groupe Hospitalier Paris Centre Cochin-Hôtel Dieu-Broca, Service de Bactériologie-CNR Streptocoques, Paris, France.
authors.forename: Philippe
authors.identifier: http://orcid.org/0000-0003-0306-8759
authors.initials: P
authors.lastname: Morand
authors.affiliation: Sorbonne Université, UPMC Université Paris 06, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.|AP-HP, Groupe hospitalier Pitié Salpêtrière, Laboratoire de Virologie, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Désiré
authors.affiliation: Sorbonne Université, UPMC Université Paris 06, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.|AP-HP, Groupe hospitalier Pitié Salpêtrière, Laboratoire de Virologie, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Sayon
authors.affiliation: Service de Bactériologie-Hygiène hospitalière, CHU de Nantes, Nantes, France.
authors.forename: Stéphane
authors.identifier: http://orcid.org/0000-0003-3176-8111
authors.initials: S
authors.lastname: Corvec
authors.affiliation: UMR8126, Institut Gustave Roussy, Villejuif, France.
authors.forename: Jöel
authors.initials: J
authors.lastname: Raingeaud
authors.affiliation: Sorbonne Université, UPMC Université Paris 06, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.|AP-HP, Groupe hospitalier Pitié Salpêtrière, Laboratoire de Virologie, Paris, France.
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
authors.affiliation: Sorbonne Université, UPMC Université Paris 06, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.|AP-HP, Groupe hospitalier Pitié Salpêtrière, Laboratoire de Virologie, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
authors.affiliation: CHU, service de dermatologie, CIC, Hôtel Dieu, Nantes, Hôtel Dieu, Nantes, France.
authors.forename: Amir
authors.initials: A
authors.lastname: Khammari
authors.affiliation: Université Sorbonne Paris Descartes, Faculté de Médecine, INSERM, Institut Cochin, Laboratoire de Dermatologie-CNR Syphilis, Paris, France.|AP-HP, Groupe Hospitalier Paris Centre Cochin-Hôtel Dieu-Broca, Service d'Immunologie Biologique, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Batteux
authors.affiliation: CHU, service de dermatologie, CIC, Hôtel Dieu, Nantes, Hôtel Dieu, Nantes, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Dréno
authors.affiliation: Université Sorbonne Paris Descartes, Faculté de Médecine, INSERM, Institut Cochin, Laboratoire de Dermatologie-CNR Syphilis, Paris, France.|AP-HP, Groupe Hospitalier Paris Centre Cochin-Hôtel Dieu-Broca, Service de Dermatologie-Vénéréologie, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dupin
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007249:Inflammation / Q000382:microbiology; D016209:Interleukin-8 / Q000096:biosynthesis; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011425:Propionibacterium acnes / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D013045:Species Specificity; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D016209:Interleukin-8; D051195:Toll-Like Receptor 2