However, epithelial cell death or an exaggerated immune response from macrophages can exacerbate pathological progression during infection.[23, 24] This study demonstrates that activation of HCAR2 in S. aureus‐infected mMECs leads to a reduction in CMPK2/mtDNA expression, which in turn inhibits NLRP3 inflammasome activation and mitigates cell pyroptosis. The gene discussed is CMPK2; the disease is infection.