1019 Cutibacterium acnes modulates the Pam3Csk4-induced innate immune responses in human keratinocytes

Various insults can trigger innate immune activation through pattern recognition receptors(PRRs) in different cell types. These leave lasting epigenetic changes, and affected cells undergo cellular reprogramming, resulting altered responsiveness to subsequent encounters. This is an adaptive response of the system called memory(IIM). We were interested whether Cutibacterium acnes (C. acnes) may initiate similar events keratinocytes. used C. for primary training, after five days rest, Pam3Csk4 (TLR1/2 agonist) secondary induction normal human epidermal keratinocyte (NHEK) HaCaT cells. The mRNA expression several immune-related genes (e.g., TNFa, IL-8, SOCS1, TNFAIP3, TNIP1) increased Pam3Csk4-induced trained cells, compared Pam3Csk4-induced, untrained ones, suggestive training-like IIM processes. Expression differences also observed NHEK but their direction was not same originating from body parts. found statistically significantly higher TNFa levels breast region (NHEK-B), lower ones abdominal (NHEK-A) samples, indicative training vs., tolerance events, respectively. global 5-methylcytosine (5-mC) content genomic DNA isolated these samples control (untrained, uninduced) NHEK-B NHEK-A even 5 resting. Previous treatment led a marked sustained decrease cultures no changes ones. Members our microbiota modify that profoundly affects cutaneous responses vitro possibly vivo. Epigenetic representing skin regions arise due variations inhabiting composition.