Our previous data has demonstrated that P. acnes clinical isolates associated with healthy skin (PH) and isolates associated with acne (PA) were found to induce distinct immune responses, leading to the secretion of pro-inflammatory cytokines mediated by toll-like receptor 2 (TLR2) and NLRP3 within antigen presenting cells (APCs). However, the vast majority of the bacterial ligands responsible for these interactions are currently unknown. The purpose of this study was to investigate and identify potential P. acnes components implicated in the induction of inflammatory responses, and to test whether these components illicit a differential outcome with respect to the two healthy and acne phylotype groups. Bacterial derived carbohydrate components extracted from PA clinical isolates induced elevated levels of IL-6 and IL-17 after stimulation of PBMCs, as compared to their healthy PH counterparts. Sodium meta-periodate can be used to oxidize the carbohydrate moiety of glycoproteins and allows for modification of carbohydrate side chains. After our carbohydrate components were oxidized with sodium meta-periodate, those treated carbohydrates were used to stimulate PBMCs; PBMCs stimulated from the PA periodate-treated components showed a greater reduction in IL-6 production than PBMCs stimulated from the PH periodate-treated components. These results suggest that carbohydrates from PA strains play an important role in the innate immune response. Additionally, real-time polymerase chain reaction (RT-PCR) revealed that there was greater expression of both IL-6 and IL-17 genes after PBMCs were stimulated by PA carbohydrate components than when stimulated from PH carbohydrate components. High performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) monosaccharide analysis of the carbohydrate components demonstrated that the PH phylotype carbohydrates contained a high concentration of galactose and low concentration of glucose, whereas the PA phylotypes conversely contained low galactose and relatively higher levels of glucose moieties. Further linkage analysis and classification of these components via GC-MS revealed that they have distinct characteristics. Taken together, our data suggests for the very first time that the carbohydrate components of diseased-associated P. acnes strains may serve as potential ligands implicated in the induction of the inflammatory response that plays a role in the pathogenesis of acne vulgaris.