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This study compared juvenile and adult mice with MRMP infection to identify age\u2010dependent immune features linked to lung injury and establish a relevant animal model for pediatric research.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Three\u2010week\u2010old (juvenile) and 8\u2010week\u2010old (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\u2010plex assay. High\u2010dimensional immune mapping of the spleen was performed by cytometry by time\u2010of\u2010flight mass spectrometry (CyTOF). Integrated analyses including sparse partial least squares\u2010discriminant analysis (sPLS\u2010DA), correlation heatmaps, and KEGG pathway enrichment were created to explore associations among differential immune subsets, inflammatory mediators, and\n                      <jats:italic>M. pneumoniae<\/jats:italic>\n                      pneumonia (MPP) phenotypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No statistically significant differences in bacterial load were observed among the MRMP\u2010infected juvenile (Juv+MRMP) and MRMP\u2010infected adult (Ad+MRMP) groups (\n                      <jats:italic>p<\/jats:italic>\n                      &gt;\u20090.05). 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\u201017A, IL\u20101\u03b2, IL\u201027) 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 (\n                      <jats:italic>p<\/jats:italic>\n                      &lt;\u20090.05); while adaptive immune responses were impaired, characterized by reduced proportions of CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells and Treg cells, and maintained a high reserve of na\u00efve Th cells compared with those in adult mice, along with elevated proportions of activated Tc cells (CD69\n                      <jats:sup>+<\/jats:sup>\n                      Tc) (\n                      <jats:italic>p<\/jats:italic>\n                      &lt;\u20090.05). Correlation analysis revealed that age and infection status are key factors driving host immune variability. M2 macrophages and NK cells were potentially associated with lung tissue pathology scores. Pathogen load correlates with both initial immune cells (CD24\n                      <jats:sup>+<\/jats:sup>\n                      na\u00efve Th, CD24\n                      <jats:sup>+<\/jats:sup>\n                      na\u00efve Tc) and effector immune cells (neutrophils, monocytes, CD69\n                      <jats:sup>+<\/jats:sup>\n                      Tc), which may contribute to a Th1\u2010type inflammatory response involving CCL2 and CCL4. Feedback\u2010upregulated Treg cells may also aid pathogen clearance by promoting IL\u201010 expression. Leukocyte migration and granulocyte chemotaxis were potentially associated with age\u2010dependent differences in inflammatory immune responses between juvenile and adult mice post\u2010MRMP infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The severity of pediatric MRMP infection may be correlated with age\u2010associated immune dysregulation\u2014characterized by heightened innate activation with insufficient adaptive regulation\u2014rather than by bacterial load alone. The three\u2010week\u2010old 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70231","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:25:46Z","timestamp":1785302746000},"page":"1489-1506","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Age\u2010associated immune dysregulation links to disease severity in macrolide\u2010resistant\n                    <i>Mycoplasma pneumoniae<\/i>\n                    pneumonia: Insights from a comparative juvenile\u2013adult mouse model"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6839-5764","authenticated-orcid":false,"given":"Xuejun","family":"Li","sequence":"first","affiliation":[{"name":"Pediatric Hospital 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