Innate and adaptive immunity pathways linking Mycoplasma pneumoniae to pediatric asthma phenotypes.

UNLABELLED: Mycoplasma pneumoniae (Mp) is repeatedly detected during pediatric wheeze and asthma exacerbations, but its clinical significance depends on the host-response context. This review evaluates the clinical and mechanistic evidence linking Mp to pediatric asthma phenotypes and examines approaches for distinguishing biologically meaningful infection from incidental detection. We narratively synthesized clinical, experimental, immunological, toxin, and proteomic literature addressing Mp-associated wheeze, asthma exacerbation, epithelial injury, allergic amplification, and inflammatory endotyping. Evidence was distinguished by population and experimental system. Experimental studies show that Mp adheres to airway epithelium; disrupts mucociliary function; activates TLR2/TLR4, NF-κB, autophagy, and inflammasome pathways; and promotes cytokine networks that overlap with allergic asthma. In experimental allergic-airway models, epithelial alarmins, IgE responses, mast cells, and type 2 inflammation may amplify Mp-driven signals, whereas IL-23/IL-17 pathways recruit neutrophils and suggest mixed endotypes; altered corticosteroid responsiveness has not been established in pediatric Mp-associated asthma. CARDS toxin induces eosinophilic inflammation, mucus metaplasia, airway hyperresponsiveness, functional IgE responses, and worsening allergen-driven disease in experimental models. Upper-airway PCR positivity, however, may reflect carriage or prolonged detection rather than active lower-airway infection.

CONCLUSION: Quantitative pathogen testing, paired serology, viral co-detection, age, atopy, microbiome context, and host-response biomarkers merit integrated evaluation in research. Proteomic and multi-omics signatures may support precision endotyping, improve causal attribution, and strengthen pediatric asthma trial design. Their diagnostic and treatment-predictive value remains unvalidated.

WHAT IS KNOWN: • M. pneumoniae is linked to pediatric wheeze and asthma exacerbations, but upper-airway PCR may reflect carriage rather than active lower-airway infection. • Epithelial injury, type 2/Th17 responses, and CARDS toxin can promote asthma-like inflammation in experimental systems.

WHAT IS NEW: • This review integrates diagnostic attribution, toxin biology, immune crosstalk, and proteomic endotyping in one pediatric framework. • It proposes an unvalidated combined pathogen-load and host-response assessment to investigate clinically meaningful M. pneumoniae-driven endotypes and guide trials.