Schematic representation of the role of neutrophil and macrophages in DADA2. Due to the lack of ADA2 activity in patients with DADA2, extracellular adenosine may accumulate. Elevated concentrations of adenosine can engage A₁AR and/or A₃AR in neutrophils leading to NET formation. In addition, LDGs present in patients with DADA2 release NETs spontaneously. Both sources of NETs can activate macrophages, leading to NF-κB translocation to the nucleus and activation of proinflammatory cytokines such as TNF-α and IL-6, among others. In turn, TNF-α can prime neutrophils to undergo further NETosis, leading to a vicious cycle.