Innate immune receptors on antigen-presenting cells activated by BCG (PRRs)

Innate immune receptors on antigen-presenting cells (APCs), such as macrophages and dendritic cells, serve as the primary sensors for Bacillus Calmette-Guérin (BCG) (Source: NIH, PMC6522662). These receptors, collectively known as Pattern Recognition Receptors (PRRs), include Toll-like receptors (TLR2, TLR4, TLR9), NOD-like receptors (specifically NOD2), and C-type lectin receptors (Dectin-1, Mincle, Mannose receptor) (Source: NIH, PMC6522662; Journal of Translational Medicine, 10.1186/s12967-023-03968-3). Upon binding to BCG's cell wall components like lipomannan and muramyl dipeptide, these receptors trigger signaling cascades (e.g., MyD88 and NF-κB pathways) that lead to the production of pro-inflammatory cytokines and the maturation of APCs (Source: MDPI, 10.3390/cells10040883). This activation is crucial for the induction of both adaptive Th1/Th17 immune responses and trained immunity, a state of long-term innate immune memory characterized by epigenetic and metabolic reprogramming (Source: Journal of Translational Medicine, 10.1186/s12967-023-03968-3). Therapeutically, the activation of these receptors by BCG is the cornerstone of its use in treating non-muscle invasive bladder cancer and its potential role in providing non-specific protection against various infections (Source: NIH, PMC6522662).

Other names

Pattern recognition receptorsPRRsBCG receptorsInnate sensing receptorsToll-like receptorsNOD-like receptorsC-type lectin receptors

BCG and its cell wall components act as agonists for multiple pattern recognition receptors (PRRs) on antigen-presenting cells. Activation of Toll-like receptors (TLR2, TLR4, TLR9) and NOD2 triggers intracellular signaling pathways, primarily MyD88 and NF-κB, which induce the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. This pro-inflammatory environment promotes the maturation of dendritic cells and macrophages, enhances antigen presentation, and drives a Th1-polarized adaptive immune response. Additionally, NOD2 activation is a key driver of trained immunity, leading to epigenetic modifications (e.g., H3K4me3) and metabolic shifts (e.g., increased glycolysis) that provide long-term enhanced innate immune responsiveness (Source: NIH, PMC6522662; Journal of Translational Medicine, 10.1186/s12967-023-03968-3).