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<i>Cutibacterium acnes</i> (<i>C. acnes</i>) has been implicated in inflammatory acne where highly mutated Christie–Atkins–Munch–Petersen factor (CAMP)1 displays strong toll like receptor (TLR)-2 binding activity. Using specific antibodies, we showed that CAMP1 production was independent of <i>C. acnes</i> phylotype and involved in the induction of inflammation. We confirmed that TLR-2 bound both mutated and non-mutated recombinant CAMP1, and peptide array analysis showed that seven peptides (A14, A15, B1, B2, B3, C1 and C3) were involved in TLR-2 binding, located on the same side of the three-dimensional structure of CAMP1. Both mutated and non-mutated recombinant CAMP1 proteins induced the production of C-X-C motif chemokine ligand interleukin (CXCL)8/(IL)-8 in vitro in keratinocytes and that of granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor (TNF)-α, IL-1β and IL-10 in ex vivo human skin explants. Only A14, B1 and B2 inhibited the production of CXCL8/IL-8 by keratinocytes and that of (GM-CSF), TNF-α, IL-1β and IL-10 in human skin explants stimulated with rCAMP1 and <i>C. acnes</i>. Following pretreatment with B2, RNA sequencing on skin explants identified the 10 genes displaying the strongest differential expression as <i>IL6</i>, <i>TNF</i>, <i>CXCL1</i>, <i>CXCL2</i>, <i>CXCL3</i>, <i>CXCL8</i>, <i>IL-1β</i>, chemokine ligand (<i>CCL</i>)<i>2</i>, <i>CCL4</i> and colony stimulating factor (<i>CSF</i>)<i>2</i>. We, thus, identified a new CAMP1-derived peptide as a TLR-2 modulator likely to be a good candidate for clinical evaluation.