Gut pathogen Clostridium symbiosum rewires macrophage succinylation to drive enteric neuron loss in inflammatory bowel disease Zhao et al. identify an IBD-enriched gut pathogen, Clostridium symbiosum, that promotes enteric neuron loss and colitis. C. symbiosum-derived succinate rewires macrophage glycolytic metabolism to sustain IL-1β signaling, thereby activating neuronal NLRP3 inflammasomes and driving neuron loss. Targeting C. symbiosum with a phage-derived endolysin preserves enteric neurons and alleviates intestinal inflammation.

#WeekendRead! #EveryCellIsAnImmuneCell! #InflammasomePower! #ImmunometabolismPower! Zhao &co show @cp-cellhostmicrobe.bsky.social that a clostridium enriched in #IBD exacerbates colitis via boosting #glycolysis & IL1b by macrophages & activating NLRP3 in enteric #neurons, causing their loss!

A metabolic alarmin from keratinocytes potentiates systemic humoral immunity - Nature Farnesyl pyrophosphate—a mevalonate pathway metabolic intermediate—is an endogenous alarmin that enhances IgG antibody responses through keratinocyte-derived IL-6 and CCL20.

#WeekendRead! #ImmunometabolismPower! #EveryCellIsAnImmuneCell! Ji, Zhang, Lu, Liu &co show @nature.com that infection, irradiation, or lupus #SLE induce a mevalonate intermediates that drives IL6 & CCL20 by #keratinocytes via NFAT to potentate antibody production!

Aerobic glycolysis promotes NLRP3 inflammasome activation via NLRP3 lactylation Liu et al. reveal that lactate, an aerobic glycolysis product, promotes NLRP3 inflammasome activation and pyroptosis. NLRP3 is identified as a target of lactylation, and K24 and K565 have potential to...

#WeekendRead! #ImmunometabolismPower! #InflammasomePower! Liu, Yin &co show @cp-cellchembiol that lactate downstream of aerobic glycolysis is used to directly lactylates NLRP3 increasing ASC recruitment and inflammasome activation, which exacerbates lethality in sepsis! www.cell.com/cell-chemica...

A non-canonical immunometabolic function of BRD3 during sepsis Wang et al. uncover a central role for BRD3 in driving harmful immune responses during sepsis. Blocking BRD3, either genetically or with the drug OTX015, protects mice from death. In patients, higher ...

#WeekendRead! #ImmunometabolismPower! #MoreThanItaconate! Wang, Tang, Kang &co show @cp-devcell.bsky.social that BRD3 induces ACOD1 via its kinase, rather than epigenetic, activity to potentiate inflammation during sepsis in a -partially- itaconate-independent manner!
www.cell.com/developmenta...

Immunometabolic reprogramming of macrophages by gut microbiota-derived cadaverine controls colon inflammation de Oliveira Formiga et al. present that gut-microbiota-derived cadaverine reprograms macrophage energy metabolism in a concentration-dependent fashion, promoting either anti- or pro-inflammatory immun...

#WeekendRead! #ImmunometabolismPower! Formiga, Sokol &co show @cp-cellhostmicrobe.bsky.social that #microbiota derived cadaverine 🧟‍♂️ controls macrophage metabolism & gut inflammation. Low 🧟‍♂️ activates NRF2 promoting OXPHOS & homeostasis, while high 🧟‍♂️ drives glycolysis & intestinal inflammation 🔥 !!

Epigenetic silencing of interleukin-10 by host-derived oxidized phospholipids supports a lethal inflammatory response to infections Phagocytes initiate immunity to invading microorganisms by detecting pathogen-associated molecular patterns via pattern recognition receptors. Pathoge…

💥 #ImmunometabolismPower! Excited to have this officially out @cp-immunity.bsky.social 💥 We show that pathogens induce the host to produce oxidized lipids which rewire the #metabolism of #macrophages, causing #epigenetic modifications which dampen anti-inflammatory IL-10, exacerbating #inflammation!

The source of dietary fat influences anti-tumour immunity in obese mice - Nature Metabolism This study shows that animal-based high-fat diets accelerate tumour growth and impair anti-tumour response to melanoma in obese mice, whereas plant-based high-fat diets do not.

#WeekendRead! #ImmunometabolismPower! Kunkemoeller @hannahprendeville.bsky.social @lydialynch.bsky.social &co show @natmetabolism.nature.com that not all fats are equal & that animal, & not plant, fats drive immune suppressive metabolites dampening NK & T cell anti #tumor responses!

Lactate signalling leads to aggregation of immune-inflammatory hotspots and SLC5A12 blockade promotes their resolution - Nature Metabolism Certo, Pontarini et al. provide insight into the metabolic requirements of ectopic lymphoid structure (ELS) assembly in the context of autoimmunity, and show that blocking lactate uptake by SLC5A12 of...

#ImmunometabolismPower! Bombardieri, Mauro, Certo &co show @natmetabolism.nature.com that #lactate drives the formation of ectopic lymphoid structures which sustain #autoimmunity/ rheumatic disease activating T/B cells & that targeting lactate uptake is protective! www.nature.com/articles/s42...

Metabolic adaptations direct cell fate during tissue regeneration - Nature Metabolic enzymes of the tricarboxylic acid cycle, such as 2-oxoglutarate dehydrogenase, are differentially expressed in absorptive and secretory lineages, guiding cell fate establishment and offering...

#WeekendRead! #ImmunometabolismPower! Lowe &co show @nature.com that alphaKetoGlutarate aKG consumption drives enterocyte differentiation while accumulation supports intestinal secretory cells! aKG supplementation can be used to favor recover from experimental #colitis!

Succinate drives gut inflammation by promoting FOXP3 degradation through a molecular switch - Nature Immunology Fang and colleagues show that the metabolite succinate can inhibit succinylation, and consequently protection from ubiquitin-mediated degradation, of the transcription factor FOXP3, with consequences ...

#WeekendRead! #ImmunometabolismPower! Wang, Fang &co show @natimmunol.nature.com that succiante is elevated in #IBD & exacerbates colitis by preventing the succinylation of FOXP3, leading to its ubiquitination & degradation, impairing Treg cell functions & favoring IL17 production!

A neuroimmune pathway drives bacterial infection Dysregulation of the dopamine-ACOD1 axis correlates with sepsis severity.

#WeekendRead #NeuroimmunologyPower #ImmunometabolismPower #NotOnlyItaconate! Kang &co show Science Advances that #dopamine inhibits ACOD1 upregulation by TLR4/CREB1, preventing ACOD1 (not itaconate) dependent PDL1 induction, protecting against inflammation-induced #immunosuppression during #sepsis!

Itaconate modulates immune responses via inhibition of peroxiredoxin 5 - Nature Metabolism Itaconate is shown to non-covalently inhibit the antioxidant enzyme peroxiredoxin 5 in macrophages, thereby modulating the production of mitochondrial peroxide and enhancing the type I interferon prod...

#ImmunometabolismPower! Artyomov, Paulenda &co show @natmetabolism.nature.com that #itaconate potentiates #interferon production & bloks late NLRP3 activation in response to microbial encounter by inhibiting a mitochondrial peroxidase thus increasing mitochondrial ROS!
www.nature.com/articles/s42...

Lactate controls cancer stemness and plasticity through epigenetic regulation Using fluorescent reporters and machine learning, Nguyen et al. traced cell types, metabolism, and lineages in tumor organoids, revealing that lactate regulates tumor development by inhibiting cancer ...

#WeekendRead. #ImmunometabolismPower! Rodriguez Colman &co show @cp-cellmetab.bsky.social that lactate maintains stemness of #cancer cells to favor tumor growth by acetylation & epigenetic activation of MYC! #ScienceSavesLives
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#ImmunometabolismPower! Rao, Feng &co show @cp-immunity.bsky.social that the pyrimidine synthesis enzyme CTPS1 also deamidates IRF3, blocking type I #interferon induction. Virus sensing activates GSK3b inhibiting CTPS1 & allowing #IFN production! www.cell.com/immunity/ful...

Join us!! #ImmunometabolismPower! 😉

Join us!! #ImmunometabolismPower!!

Platelet factor 4–induced TH1-Treg polarization suppresses antitumor immunity The tumor microenvironment (TME) contains a number of immune-suppressive cells such as T helper 1–polarized regulatory T cells (TH1-Treg cells). However, little is known about the mechanism behind the...

#ImmunometabolismPower! Kuratani, Yamamoto &co show @ Science that Arg1+ tumor-associated macrophages #TAMs secrete platelet factor-4 #PF4 in the presence of lactate/aerobic glycolysis driving pro-tumoral Th1-Treg cells that can be targeted by a blocking antibody! www.science.org/doi/10.1126/...

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#SharingIsCaring #EveryCellIsAnImmuneCell #ImmunometabolismPower! Baldwin, Gattinoni, Sengupta &co show @ Cell that bone marrow stromal cells transfer #mitochondria to CD8 T cells supercharging them & potentiating their anti-tumor functions prolonging mouse survival!
doi.org/10.1016/j.ce...