Conventional neutrophil host defense includes the recruitment cascade, chemotaxis, phagocytosis, and microbial killing. Stimulation of neutrophil receptors by microorganisms or soluble mediators evokes release of NETs. NETs trap bacteria, viruses, and fungi, thereby aiding in containing local infections. However, NET components could also contribute to maintaining an inflammatory environment, trigger autoimmunity, and activate coagulation resulting in thrombosis. These would lead to persistent inflammation and damage to the host. Chiang et al show that RvTs (derived from a common intermediate of n-3 docosapentaenoic acid) exert multipronged actions to counter aberrant neutrophil responses. Thus, RvTs, acting through unidentified G protein–coupled receptors (GPCRs), inhibit neutrophil recruitment, reduce NET formation, and enhance NET clearance by M0 macrophages. In macrophages, NET uptake is closely associated with activation of the cAMP-PKA-AMPK pathway that mediates phagocytosis. Reducing NET formation and facilitating NET clearance without hindering neutrophil phagocytosis led to timely resolution and return to homeostasis, suggesting the therapeutic potential for RvTs in pathologies associated with aberrant NET formation. AMPK, AMP-activated protein kinase; cAMP, cyclic adenosine monophosphate; IL-1β, interleukin-1β; NE, neutrophil elastase; PKA, protein kinase A; TF, tissue factor. Professional illustration by Somersault18:24.