The NLRP3 Inflammasome as a Central Driver of Mastitis Pathogenesis: A Review

Mastitis remains the most economically damaging disease of dairy production, and recent molecular work has converged on the NLRP3 inflammasome as a key integrative node of its pathogenesis. This narrative review integrates evidence published largely between 2015 and 2026 to show how diverse triggers—Staphylococcus aureus and Escherichia coli, lipopolysaccharide (LPS) and lipoteichoic acid (LTA), non-esterified fatty acids (NEFA), heat stress, environmental xenobiotics including nanoplastics, and microbiota-derived signals—may funnel into a common NLRP3–ASC–caspase-1–GSDMD axis that drives pyroptosis, blood–milk barrier disruption, and clinical disease. The review examines the potential obligatory role of reactive oxygen species (ROS), mitochondrial dysfunction, and selenoprotein-mediated redox control in licensing inflammasome assembly. It further evaluates the emerging gut–mammary and rumen–mammary axes that operate upstream of local epithelial activation. We survey a structurally diverse therapeutic landscape encompassing dietary selenium, probiotics, microbial metabolites, plant-derived nanovesicles, polyphenols, ginsenosides, and small-molecule NLRP3 antagonists, identifying recurring mechanistic motifs that suggest combinatorial regimens may yield additive benefit. Importantly, much of the evidence derives from in vitro and murine models, and we highlight the translational gaps that must be bridged before clinical application in dairy cattle. Finally, we map outstanding research gaps and propose priorities for translational work aimed at sustainable, antibiotic-sparing management of bovine mastitis.