How does the immune system distinguish bacterial DNA from our own? This comprehensive review explores the role of unmethylated CpG motifs, prevalent in bacterial DNA but rare in vertebrate DNA, as potent immune stimulators. These motifs activate host defense mechanisms, triggering both innate and acquired immune responses through Toll-like receptor (TLR) 9 recognition. TLR-9 activation leads to cellular redox balance changes and induction of signaling pathways involving mitogen-activated protein kinases (MAPKs) and NFκB. Cells expressing TLR-9, such as plasmacytoid dendritic cells (PDCs) and B cells, produce Th1-like proinflammatory cytokines, interferons, and chemokines. Certain CpG motifs (CpG-A) are particularly effective at activating NK cells and inducing IFN-α production by PDCs, while others (CpG-B) are potent B cell activators. CpG-induced immune activation offers protection against a wide range of pathogens and demonstrates therapeutic potential in cancer and allergy models. CpG ODN also enhance acquired immune responses, improving prophylactic and therapeutic vaccination strategies, making them valuable tools in immunotherapy and vaccine development.
This review, published in the Annual Review of Immunology, directly aligns with the journal's focus on comprehensive and critical analyses of significant topics in immunology. The detailed exploration of CpG motifs and their immune effects fits perfectly within the journal's scope, providing a valuable overview for immunologists and related researchers.