A study by Hessel et al. (page 1563) explains how a potent immune activator shuts down allergic inflammation. CpG-rich DNA sequences, common in microbial DNA, are best known as agents that bind to the innate receptor Toll-like receptor (TLR)-9 on immune cells, triggering their activation and alerting the host to the pathogenic invasion.
Clinicians have taken advantage of the immune-activating qualities of CpG-rich DNA molecules, which are in a clinical trial as immunostimulatory agents such as adjuvants. However, treatment with these synthetic DNAs also inhibits allergic airway inflammation in mice, a phenomenon commonly attributed to the CpG-induced production of T helper (Th)-1–promoting cytokines, which counteract the effects of allergy-promoting Th2 cytokines.
But Hessel and colleagues now show that antiallergy CpG DNA treatment works not by antagonizing the effects of Th2 cytokines, but by preventing the Th2 response from ever getting started. CpG treatment...
