Itaconate as an immunometabolic hub in host-pathogen interactions: Mechanisms, resistance, and therapeutic opportunities.
- 1Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
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.
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BibTeX
@article{zuo2026itaconate,
title = {{Itaconate as an immunometabolic hub in host-pathogen interactions: Mechanisms, resistance, and therapeutic opportunities.}},
author = {Wei Zuo and Xinhui Wang and Jiaxiang Sun and Weiqi Guo and Beibei Zhang and Xinyu Wang and Jiangang Hu and Jingjing Qi and Mingxing Tian and Lei Deng and Shaohui Wang and Yanqing Bao},
journal = {Virulence},
year = {2026},
month = oct,
doi = {10.1080/21505594.2026.2749933},
url = {https://europepmc.org/article/MED/42881518},
note = {CC BY},
}
RIS
TY - JOUR
TI - Itaconate as an immunometabolic hub in host-pathogen interactions: Mechanisms, resistance, and therapeutic opportunities.
AU - Wei Zuo
AU - Xinhui Wang
AU - Jiaxiang Sun
AU - Weiqi Guo
AU - Beibei Zhang
AU - Xinyu Wang
AU - Jiangang Hu
AU - Jingjing Qi
AU - Mingxing Tian
AU - Lei Deng
AU - Shaohui Wang
AU - Yanqing Bao
PY - 2026
DA - 2026/10/15
JO - Virulence
DO - 10.1080/21505594.2026.2749933
UR - https://europepmc.org/article/MED/42881518
AB - 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.
SN - 2150-5594
SN - 2150-5608
ER -