Immunostimulatory DNA induces degranulation and NADPH-oxidase activation in human neutrophils while concomitantly inhibiting chemotaxis and phagocytosis

Abstract

We examined the effects of oligodeoxynucleotides (ODN) with different structures and sequences on human neutrophil function. In lymphocytes and monocytes, the CpG-mediated immunostimulation is dependent on motif content, flanking sequences and DNA backbone composition. In neutrophils, however, native phosphodiester ODN were without effect regardless of CpG content, while backbone-substituted phosphorothioate ODN (PS-ODN) modulated neutrophil function in a sequence-independent manner. The neutrophil respiratory burst and degranulation of the specific and gelatinase granules were markedly increased by PS-ODN, as was the shedding of L-selectin. In contrast, neutrophil chemotaxis and phagocytosis were inhibited by PS-ODN. In summary, PS-ODN have both stimulatory and inhibitory effects on neutrophil function. This impact of PS-ODN on neutrophil function is unique and distinct from that exerted on other immune cells, with respect to both the identity of the activating DNA molecules and the regulation of the effector functions. These findings may have implications for the development of DNA-based immunotherapy and vaccination.