Fig. 6.

Model for activity of DNase in ABM. In ABM, in the absence of DNase (left panel), invasion of pneumococci into the CSF triggers neutrophil migration into the CNS resulting in pleocytosis and massive neutrophil extracellular trap (NET) formation. The trapped bacteria survive in the NETs because they are shielded from neutralization by cationic antimicrobial peptides and anionic extracellular DNA and are protected from phagocytosis by neutrophils. In the presence of DNase (right panel), the NETs are resolved due to degradation of extracellular DNA. (1) This generates antimicrobial DNA fragments and frees antimicrobial proteins, which exert bactericidal/bacteriostatic effects, leading to increased extracellular killing of bacteria. (2) The degradation of DNA also makes bacteria more accessible to intact neutrophils, leading to increased phagocytosis. (3) This increased contact with bacteria leads to activation of the respiratory burst pathway within the neutrophil, generating various peroxidated products and hypochlorite (HOCl), leading to increased intracellular killing of the bacteria