{
  "abstract": "Paediatric refractory Mycoplasma pneumoniae pneumonia (RMPP) is a heterogeneous syndrome in which persistent microbial stimulation, dysregulated host immunity and evolving airway injury may coexist despite macrolide treatment. This review integrates clinical, experimental and multi-omics evidence to examine RMPP through an immunometabolic framework. Mycoplasma pneumoniae reprograms airway epithelial cells, macrophages and neutrophils by altering glycolysis, mitochondrial and redox signalling, autophagy and lipid and amino-acid metabolism. These responses can support early antimicrobial defence yet become maladaptive when inflammatory output is uncoupled from bacterial clearance. Epithelial ATP-dependent signalling, macrophage inflammasome activation, neutrophil aconitate decarboxylase 1 (ACOD1; historically termed immune-responsive gene 1 [IRG1])-itaconate activity and extracellular trap accumulation illustrate this context-dependent transition. Adaptive immune remodelling, compartment-specific Th17-regulatory T-cell imbalance and incomplete mucosal antibody protection may further sustain disease. Emerging metabolomic, lipidomic, microbiome and single-cell studies support biological heterogeneity but remain predominantly cross-sectional and cannot distinguish causal drivers from consequences of severe disease or treatment. Current mechanistic evidence is strongest for epithelial glycolysis and the neutrophil ACOD1-itaconate axis in experimental M. pneumoniae systems, whereas direct cell-resolved functional validation in paediatric RMPP remains limited, and ferroptosis and several proposed therapeutic targets remain provisional. We therefore present immunometabolic states as a hypothesis-generating framework rather than as validated endotypes. Future studies should determine whether dynamic combinations of pathogen burden, cell-specific metabolic function, inflammatory activity and anatomical injury reproducibly identify biological states that precede progression and predict differential treatment response. Longitudinal, cell-resolved studies integrating metabolic flux, pathogen trajectories, treatment exposure and anatomical evolution are required before these candidate states can support mechanism-informed clinical stratification.",
  "abstract_shown": true,
  "affiliations": [
    "Diagnosis and Treatment Center for Children, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, China",
    "Department of Pediatrics, The Third Clinical Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, China"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jingjing Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Shengtao Cui"
    },
    {
      "affs": [
        0
      ],
      "name": "Wei Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Jian Liu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/apqe2d78mg5xn.bib",
  "cited_by": 0,
  "doi": "10.3389/fcimb.2026.1954451",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fcimb.2026.1954451/full",
  "id": "apqe2d78mg5xn",
  "issns": [
    "2235-2988"
  ],
  "landing_url": "https://doi.org/10.3389/fcimb.2026.1954451",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QR1-502"
    ],
    [
      "openalex",
      "2404|Microbial infections and disease research"
    ]
  ],
  "openalex": "W7224086301",
  "pdf_url": "https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2026.1954451/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": "Frontiers Media S.A.",
  "ris": "https://research.draconitic.com/paper/apqe2d78mg5xn.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T14:22:07Z",
      "native_id": "23e8c89a5d3e409ca55f949eec11d053",
      "source": "doaj",
      "url": "https://doi.org/10.3389/fcimb.2026.1954451"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2404|Microbial infections and disease research",
      "subfield": "microbiology"
    }
  ],
  "title": "Host immunometabolic reprogramming in paediatric refractory mycoplasma pneumoniae pneumonia: cellular circuits, multi-omics signatures, and translational opportunities",
  "title_text": "Host immunometabolic reprogramming in paediatric refractory mycoplasma pneumoniae pneumonia: cellular circuits, multi-omics signatures, and translational opportunities",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T14:22:07Z",
  "url": "https://research.draconitic.com/paper/apqe2d78mg5xn",
  "venue": "Frontiers in Cellular and Infection Microbiology",
  "versions": []
}