ArticleAnimal models and experimental medicine2026
Age-associated immune dysregulation links to disease severity in macrolide-resistant Mycoplasma pneumoniae pneumonia: Insights from a comparative juvenile-adult mouse model.
Article in Animal models and experimental medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundMacrolide-resistant mycoplasma pneumoniae (MRMP) infections are more common and severe in children, indicating that age-related immune dysregulation affects disease outcomes, yet the underlying mechanisms remain unclear and suitable pediatric models are lacking. This study compared juvenile and adult mice with MRMP infection to identify age-dependent immune features linked to lung injury and establish a relevant animal model for pediatric research.
methodsThree-week-old (juvenile) and 8-week-old (adult) BALB/c mice were infected with MRMP. Pathological phenotypes included lung index, bacterial load, and lung histopathology scores. Serum inflammatory storm profiles were characterized using the Olink 48-plex assay. High-dimensional immune mapping of the spleen was performed by cytometry by time-of-flight mass spectrometry (CyTOF). Integrated analyses including sparse partial least squares-discriminant analysis (sPLS-DA), correlation heatmaps, and KEGG pathway enrichment were created to explore associations among differential immune subsets, inflammatory mediators, and M. pneumoniae pneumonia (MPP) phenotypes.
resultsNo statistically significant differences in bacterial load were observed among the MRMP-infected juvenile (Juv+MRMP) and MRMP-infected adult (Ad+MRMP) groups (p > 0.05). However, the Juv+MRMP group exhibited significantly higher lung indices and more severe pulmonary histopathological damage, indicating a dissociation between bacterial burden and tissue injury. Olink analysis revealed significantly higher levels of serum chemokines (CCL2, CCL12, CCL22) and proinflammatory cytokines (IL-17A, IL-1β, IL-27) in the Juv+MRMP group than in the Ad+MRMP group. CyTOF analysis revealed a starkly different immune landscape: Juvenile mice exhibited excessive innate immune activation, with significant increases in neutrophil and monocyte infiltration, as well as elevated proportions of M2 macrophages and NK cells (p < 0.05); while adaptive immune responses were impaired, characterized by reduced proportions of CD4
conclusionThe severity of pediatric MRMP infection may be correlated with age-associated immune dysregulation-characterized by heightened innate activation with insufficient adaptive regulation-rather than by bacterial load alone. The three-week-old juvenile mouse model appears to recapitulate key features of MRMP infection in children and could potentially serve as a useful platform for mechanistic and intervention studies.
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