TNF and type I IFN induction of the IRG1-itaconate pathway restricts Coxiella burnetiireplication within mouse macrophages
Boyer, M.; Lopes Fischer, N.; Shin, S.
Show abstract
The intracellular Gram-negative bacterium Coxiella burnetii replicates within macrophages and causes a zoonotic disease known as Q fever. In murine macrophages, the cytokine tumor necrosis factor (TNF) is critical for restriction of intracellular C. burnetii replication. Here, we show that TNF collaborates with type I interferon (IFN) signaling for maximal control of C. burnetii. We found that TNF and type I IFN upregulate the expression of the metabolic enzyme immune responsive gene 1 (IRG1), also known as cis-aconitate decarboxylase 1 (ACOD1), and that IRG1 is required to restrict C. burnetii T4SS translocation and replication within macrophages. Further, we show that itaconic acid, the metabolic product of IRG1, restricts C. burnetii replication both intracellularly and in axenic culture. These data reveal that TNF and type I IFN upregulate the IRG1-itaconate pathway to restrict intracellular C. burnetii replication within murine macrophages.
Matching journals
The top 2 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- NLRP11 is required for canonical NLRP3 and non-canonical inflammasome activation during human macrophage infection with mycobacteria 97%
- Bacterial strain-dependent dissociation of cell recruitment and cell-to-cell spread in early M. tuberculosis infection 97%
- Cyclic di-AMP inhibits Listeria monocytogenes thymineless death during infection 96%
Similar papers in this journal
Similar papers in this journal
- The opportunistic intracellular bacterial pathogen Rhodococcus equi elicits type I interferons by engaging cytosolic DNA sensing in macrophages 98%
- IFN-γ-independent control of M. tuberculosis requires CD4 T cell-derived GM-CSF and activation of HIF-1α 97%
- Toxoplasma GRA15 and GRA24 are important activators of the host innate immune response in the absence of TLR11 96%
Similar papers in this journal
- RIPK1 activates distinct gasdermins in macrophages and neutrophils upon pathogen blockade of innate immune signalling 96%
- The C terminus of the mycobacterium ESX-1 secretion system substrate ESAT-6 is required for phagosomal membrane damage and virulence 96%
- TLR4 signaling and macrophage inflammatory responses are dampened by GIV/Girdin 94%
Similar papers in this journal
- The Shigella flexneri effector IpaH1.4 facilitates RNF213 degradation and protects cytosolic bacteria against interferon-induced ubiquitylation 96%
- Over-expression Screen of Interferon-Stimulated Genes Identifies RARRES3 as a Restrictor of Toxoplasma gondii Infection 95%
- Impaired fatty acid import or catabolism in macrophages restricts intracellular growth of Mycobacterium tuberculosis 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.