Diagenode

The Itaconate Pathway Is a Central Regulatory Node Linking Innate Immune Tolerance and Trained Immunity


Domínguez-Andrés Jorge, Novakovic Boris, Li Yang, Scicluna Brendon P., Gresnigt Mark S., Arts Rob J.W., Oosting Marije, Moorlag Simone J.C.F.M., Groh Laszlo A., Zwaag Jelle, Koch Rebecca M., ter Horst Rob, Joosten Leo A.B., Wijmenga Cisca, Michelucci Ales

Sepsis involves simultaneous hyperactivation of the immune system and immune paralysis, leading to both organ dysfunction and increased susceptibility to secondary infections. Acute activation of myeloid cells induced itaconate synthesis, which subsequently mediated innate immune tolerance in human monocytes. In contrast, induction of trained immunity by b-glucan counteracted tolerance induced in a model of human endotoxemia by inhibiting the expression of immune-responsive gene 1 (IRG1), the enzyme that controls itaconate synthesis. b-Glucan also increased the expression of succinate dehydrogenase (SDH), contributing to the integrity of the TCA cycle and leading to an enhanced innate immune response after secondary stimulation. The role of itaconate was further validated by IRG1 and SDH polymorphisms that modulate induction of tolerance and trained immunity in human monocytes. These data demonstrate the importance of the IRG1-itaconateSDH axis in the development of immune tolerance and training and highlight the potential of b-glucaninduced trained immunity to revert immunoparalysis.

Tags
Antibody
Bioruptor Plus

Share this article

Published
October, 2018

Source

Products used in this publication

  • cut and tag antibody icon
    C15410196
    H3K27ac Antibody - ChIP-seq Grade
  • cut and tag antibody icon
    C15410195
    H3K27me3 Antibody - ChIP-seq Grade
  • ChIP-seq Grade
    C15410192
    H3K36me3 Antibody - ChIP-seq Grade
  • ChIP-seq Grade
    C15410037-50
    H3K4me1 Antibody - ChIP-seq Grade
  • cut and tag antibody icon
    C15410003-50
    H3K4me3 Antibody - ChIP-seq Grade
  • cut and tag antibody icon
    C15410193
    H3K9me3 Antibody - ChIP-seq Grade
  • default alt
    C03010021-220
    DiaMag protein G-coated magnetic beads (ChIP-se...
  • Bioruptor Plus Sonication Device
    B01020001
    Bioruptor® Plus sonication device

活动

  • Long-Read Sequencing Meeting 2024
    Uppsala, Sweden
    Oct 21-Oct 23, 2024
  • NextGen Omics 2024
    London, UK
    Oct 23-Oct 25, 2024
  • FEBS 2024
    Budapest, Hungary
    Oct 28-Oct 31, 2024
  • 5th Danube Conference on Epigenetics
    Budapest, Hungary
    Oct 28-Oct 31, 2024
 查看所有活动

 


       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy