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@ARTICLE{Bruno:282549,
      author       = {Bruno, Mariolina and Kröger, Charlotte and Ferreira,
                      Anaísa V and Zhang, Bowen and Röring, Rutger J and Liu,
                      Ruiqi and van der Made, Caspar I and van Rhijn, Norman and
                      Groh, Laszlo and Klück, Viola and Janssen, Nico A F and Li,
                      Wenchao and Rosati, Diletta and Alaswad, Ahmed and Tercan,
                      Helin and Saiz, Jorge and Gonzalez-Riano, Carolina and van
                      Uelft, Martina and Gaal, Orsolya Ildiko and Müller, Sophie
                      and Ferreira, Humberto J and Warnat-Herresthal, Stefanie and
                      Becker, Matthias and Holsten, Lisa and Kraut, Michael and
                      Schulte-Schrepping, Jonas and Bonaguro, Lorenzo and
                      Händler, Kristian and Cunha, Cristina and Schmolz, Manfred
                      and Schultze, Joachim L and Joosten, Leo A B and Barbas,
                      Coral and Netea, Mihai G and Li, Yang and Aschenbrenner,
                      Anna C and Carvalho, Agostinho and van de Veerdonk, Frank L},
      title        = {{I}nterferon gamma rebalances immunopathological signatures
                      in chronic granulomatous disease through metabolic
                      rewiring.},
      journal      = {Blood advances},
      volume       = {9},
      number       = {20},
      issn         = {2473-9529},
      address      = {Washington, DC},
      publisher    = {American Society of Hematology},
      reportid     = {DZNE-2025-01312},
      pages        = {5306 - 5322},
      year         = {2025},
      abstract     = {Chronic granulomatous disease (CGD) is a primary
                      immunodeficiency characterized by recurrent life-threatening
                      infections and hyperinflammatory complications. It is caused
                      by mutations in the reduced nicotinamide adenine
                      dinucleotide phosphate (NADPH) oxidase complex and the
                      consequent loss of reactive oxygen species (ROS) production.
                      Recombinant human interferon gamma (rIFN-γ) prophylaxis
                      reduces the risk of severe infections, but the mechanisms
                      behind its efficacy in CGD are still an open question, as it
                      does not restore NADPH oxidase-dependent ROS production.
                      Here, we demonstrate that the innate immune cells of
                      patients with CGD are transcriptionally and functionally
                      reprogrammed to a hyperactive inflammatory status,
                      displaying an impaired in vitro induction of trained
                      immunity. CGD monocytes have reduced intracellular amino
                      acid concentrations and profound functional metabolic
                      defects, both at the level of glycolysis and mitochondrial
                      respiration. Ex vivo and in vivo treatments with IFN-γ
                      restored these metabolic defects and reduced excessive
                      interleukin 1β (IL-1β) and IL-6 production in response to
                      fungal stimuli in CGD monocytes. These data suggest that
                      prophylactic rIFN-γ modulates the metabolic status of
                      innate immune cells in CGD. These data shed light on the
                      effects of NADPH oxidase-derived ROS deficiency to the
                      metabolic programs of immune cells and pose the basis for
                      targeting this immunometabolic axis, potentially beyond CGD,
                      with IFN-γ immunotherapy.},
      keywords     = {Humans / Granulomatous Disease, Chronic: metabolism /
                      Granulomatous Disease, Chronic: immunology / Granulomatous
                      Disease, Chronic: drug therapy / Granulomatous Disease,
                      Chronic: pathology / Interferon-gamma: pharmacology /
                      Interferon-gamma: therapeutic use / Reactive Oxygen Species:
                      metabolism / Monocytes: metabolism / Monocytes: immunology /
                      Monocytes: drug effects / Immunity, Innate: drug effects /
                      NADPH Oxidases: metabolism / Male / Female /
                      Interferon-gamma (NLM Chemicals) / Reactive Oxygen Species
                      (NLM Chemicals) / NADPH Oxidases (NLM Chemicals)},
      cin          = {AG Aschenbrenner / AG Schultze / AG Bonaguro / AG Becker /
                      PRECISE},
      ddc          = {610},
      cid          = {I:(DE-2719)5000082 / I:(DE-2719)1013038 /
                      I:(DE-2719)1016005 / I:(DE-2719)5000079 /
                      I:(DE-2719)1013031},
      pnm          = {354 - Disease Prevention and Healthy Aging (POF4-354) / 352
                      - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-354 / G:(DE-HGF)POF4-352},
      experiment   = {EXP:(DE-2719)PRECISE-20190321},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40674716},
      pmc          = {pmc:PMC12556223},
      doi          = {10.1182/bloodadvances.2025016213},
      url          = {https://pub.dzne.de/record/282549},
}