Host immunometabolic reprogramming in paediatric refractory mycoplasma pneumoniae pneumonia: cellular circuits, multi-omics signatures, and translational opportunities
- 1Diagnosis and Treatment Center for Children, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, China
- 2Department of Pediatrics, The Third Clinical Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, China
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.
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BibTeX
@article{yang2026host,
title = {{Host immunometabolic reprogramming in paediatric refractory mycoplasma pneumoniae pneumonia: cellular circuits, multi-omics signatures, and translational opportunities}},
author = {Jingjing Yang and Shengtao Cui and Wei Li and Jian Liu},
journal = {Frontiers in Cellular and Infection Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fcimb.2026.1954451},
url = {https://doi.org/10.3389/fcimb.2026.1954451},
note = {CC BY},
}
RIS
TY - JOUR
TI - Host immunometabolic reprogramming in paediatric refractory mycoplasma pneumoniae pneumonia: cellular circuits, multi-omics signatures, and translational opportunities
AU - Jingjing Yang
AU - Shengtao Cui
AU - Wei Li
AU - Jian Liu
PY - 2026
DA - 2026/10/28
JO - Frontiers in Cellular and Infection Microbiology
DO - 10.3389/fcimb.2026.1954451
UR - https://doi.org/10.3389/fcimb.2026.1954451
AB - 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.
SN - 2235-2988
ER -