The article reviews the role of itaconate, an immune-metabolite produced by macrophages through the decarboxylation of cis-aconitate by the enzyme ACO1, in immune cell signaling and metabolic pathways. Itaconate has both antimicrobial and immunoregulatory activities, making it a promising candidate for therapeutic intervention in infections and inflammation. The review highlights the induction of ACO1 expression in macrophages by microbial pathogens and cytokines, and the subsequent production of itaconate. Itaconate modulates immune cell signaling and metabolism through various mechanisms, including inhibition of enzymes like succinate dehydrogenase (SDH) and Tet2, and post-translational modifications (PTMs) of proteins at cysteine or lysine residues. The PTM of signaling proteins such as STING, SYK, JAK1, RIPK3, and KEAP1, as well as transcription regulators like Tet2 and TFEB, and inflammasome components like NLRP3 and GSDMD, provides a biochemical basis for its immune-regulatory effects. The review also discusses the role of itaconate in neutrophils and adaptive immune responses, including its effects on T cells and antigen-presenting cells. The findings suggest that itaconate's dual role as an antimicrobial and immunoregulatory agent holds promise for the development of treatments for acute and chronic inflammatory and infectious diseases.The article reviews the role of itaconate, an immune-metabolite produced by macrophages through the decarboxylation of cis-aconitate by the enzyme ACO1, in immune cell signaling and metabolic pathways. Itaconate has both antimicrobial and immunoregulatory activities, making it a promising candidate for therapeutic intervention in infections and inflammation. The review highlights the induction of ACO1 expression in macrophages by microbial pathogens and cytokines, and the subsequent production of itaconate. Itaconate modulates immune cell signaling and metabolism through various mechanisms, including inhibition of enzymes like succinate dehydrogenase (SDH) and Tet2, and post-translational modifications (PTMs) of proteins at cysteine or lysine residues. The PTM of signaling proteins such as STING, SYK, JAK1, RIPK3, and KEAP1, as well as transcription regulators like Tet2 and TFEB, and inflammasome components like NLRP3 and GSDMD, provides a biochemical basis for its immune-regulatory effects. The review also discusses the role of itaconate in neutrophils and adaptive immune responses, including its effects on T cells and antigen-presenting cells. The findings suggest that itaconate's dual role as an antimicrobial and immunoregulatory agent holds promise for the development of treatments for acute and chronic inflammatory and infectious diseases.