TLR-2 Recognizes Propionibacterium acnes CAMP Factor 1 from Highly Inflammatory Strains

Area of Science:

• Microbiology
• Immunology
• Dermatology

Background:

• Propionibacterium acnes (P. acnes) is implicated in inflammatory acne.
• P. acnes triggers immune responses in skin cells, but specific surface protein interactions with Toll-like receptors (TLRs) were unknown.
• Previous studies showed P. acnes surface proteins induce CXCL8 production.

Purpose of the Study:

• To identify P. acnes surface proteins that interact with Toll-like receptors (TLRs).
• To characterize the identified proteins and their role in initiating inflammatory responses.
• To investigate the correlation between P. acnes strain types, protein binding, and CXCL8 production.

Main Methods:

• Far-western blotting to identify TLR2-binding proteins.
• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and N-terminal sequencing for protein identification.
• Functional assays measuring CXCL8 production and promoter activation.
• Analysis of P. acnes strains with varying CAMP1-TLR2 binding intensities.

Main Results:

• Two P. acnes surface proteins (24.5- and 27.5-kDa) were identified as binding to TLR2.
• These proteins were characterized as CAMP factor 1 (lacking its signal peptide).
• Purified CAMP factor 1 induced CXCL8 production by activating its gene promoter, and anti-TLR2 antibodies reduced this response.
• CAMP factor 1 binding to TLR2 varied among P. acnes strains, correlating with CXCL8 production levels.
• CAMP factor 1 nucleotide sequence polymorphism defined genetic groups associated with differential CAMP1-TLR2 binding and CXCL8 production.

Conclusions:

• CAMP factor 1 directly interacts with TLR2.
• This interaction amplifies inflammatory responses, suggesting CAMP factor 1 contributes to P. acnes virulence in acne.