Itaconate as an immunometabolic hub in host–pathogen interactions: Mechanisms, resistance, and therapeutic opportunities
Year: 2026
Type: article
Abstract: Produced by IRG1 in macrophages, itaconate has emerged as an immunometabolic hub at the host-pathogen interface. This review integrates itaconate's roles in antimicrobial defense. We first examine how itaconate inhibits pathogen metabolism by targeting key enzymes including isocitrate lyase, fructose-bisphosphate aldolase, and inosine monophosphate dehydrogenase. Beyond direct inhibition, itaconate reprograms host immunity through SDH suppression, Nrf2 activation, ATF3 induction, and context-dependent NLRP3 regulation, and promotes lysosomal biogenesis via TFEB. Conversely, pathogens have evolved counter strategies including enzymatic degradation, biofilm formation, and immune microenvironment remodeling. We also summarize preclinical evidence supporting itaconate and derivatives' therapeutic potential for infection-associated conditions. Finally, we appraise theoretical gaps and methodological challenges, offering guidance for future investigation in this rapidly advancing field.
Source: Virulence
Institution: Chinese Academy of Agricultural Sciences
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,557
OpenAlex ID: W7222491204