Innate and adaptive immune receptors activated by BCG

BCG (Bacillus Calmette-Guérin) is a live-attenuated vaccine derived from Mycobacterium bovis, primarily used for tuberculosis prevention and as a gold-standard intravesical immunotherapy for non-muscle invasive bladder cancer (Pettenati & Ingersoll, 2018). Its efficacy relies on the coordinated activation of a diverse array of innate and adaptive immune receptors. Innate recognition is mediated by pattern recognition receptors (PRRs) such as Toll-like receptors (TLR2, TLR4), NOD-like receptors (specifically NOD2), and C-type lectin receptors like Dectin-1 and Mincle, which detect mycobacterial cell wall components (Moliva et al., 2017). This activation triggers the release of pro-inflammatory cytokines and the recruitment of immune cells, including macrophages and natural killer cells. Furthermore, BCG induces an adaptive immune response characterized by the activation of T-cell receptors (TCRs) through the presentation of mycobacterial antigens by MHC molecules, leading to a Th1-polarized response (Redelman-Sidi et al., 2014). A key feature of BCG's action is the induction of "trained immunity," an epigenetic reprogramming of innate immune cells that enhances their response to subsequent challenges (Netea et al., 2020).

Other names

BCG-activated receptorsMycobacterial pattern recognition receptorsToll-like receptor 2 (TLR2)Toll-like receptor 4 (TLR4)NOD2 (Nucleotide-binding oligomerization domain-containing protein 2)Dectin-1 (CLEC7A)Mincle (CLEC4E)T-cell receptor (TCR)

BCG acts as a biological response modifier that binds to fibronectin in the bladder wall, is internalized by urothelial and immune cells, and activates multiple pattern recognition receptors (PRRs) including TLR2, TLR4, and NOD2. This leads to the production of Th1 cytokines (IFN-gamma, IL-12), recruitment of cytotoxic T lymphocytes and NK cells, and the induction of trained immunity through epigenetic changes in myeloid cells.