Lactobacillus helveticus GCL1815 induces Th1-skewing T-cell responses via dendritic cell activation

Recent studies have highlighted how the immunomodulatory effects of probiotics act through dendritic cell (DC) activation. Evaluation of their in vivo efficacy requires understanding their strain-specific functions, the magnitude of their activity, and the differences in active components. Although we previously identified Lactobacillus helveticus GCL1815 as having potent immunostimulatory properties, its ability to induce T cell responses, a critical function of DCs, was unclear. Accordingly, we assessed the DC-activating capacity of GCL1815 and its potential to promote T cell responses. Stimulating human monocyte-derived DCs (MoDCs) with GCL1815 resulted in upregulated expression of activation markers and a marked increase in interleukin-12 (IL-12) p70 production. Furthermore, co-culturing these stimulated MoDCs with allogeneic T cells enhanced the proliferation of both CD4⁺ and CD8⁺ T cells and significantly increased interferon-γ (IFN-γ) secretion. These findings suggest that GCL1815 enhances antigen presentation and co-stimulatory molecule expression in DCs and promotes T helper 1 (Th1)-skewing T cell responses via IL-12 production. In addition, Toll-like receptor (TLR) blockade experiments using THP-1 cells revealed that TLR2 inhibition partially suppressed IL-12p40 production, suggesting that DC activation by GCL1815 partially involves the TLR2 signaling pathway. Collectively, these results show that L. helveticus GCL1815 induces Th1-skewing T cell responses through DC activation, likely mediated by cell wall components recognized via TLR2. Previous clinical trials suggest that continuous intake of GCL1815 may reduce or alleviate common cold-like symptoms. The present findings provide mechanistic insights into the functionality of GCL1815, bridging the innate and adaptive immune responses.