Immune dysregulation in Mycoplasma pneumoniae pneumonia: Mechanistic controversies and clinical translation from inflammatory dysregulation and immune evasion to chronic injury

Xuejun Li¹Yudong Wang²Qiuyan Wang³Hongji Wu³Yong-bin YAN¹Yibai Xiong²Ying Ding^1*

• ¹Pediatric Hospital, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China
• ²Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
• ³Pediatric Medical College, Henan University of Chinese Medicine, Zhengzhou, China

Mycoplasma pneumoniae (MP) is a leading cause of pediatric community-acquired pneumonia, with clinical manifestations ranging from self-limiting disease to severe refractory pneumonia and long-term pulmonary sequelae. Three interrelated, partially overlapping yet still contested processes can explain the core pathogenic mechanisms of MP pneumonia (MPP). In the acute phase, immune dysregulation is characterized by excessive cytokine release and abnormal activation of innate and adaptive immune cells; however, the origin and regulation of this excessive inflammation remain controversial. During the immune evasion phase, MP employs multiple escape strategies, including adhesion proteins, CARDS toxins, and genomic plasticity, to circumvent host defenses, establish persistent infections, and further leave hidden dangers for acute phase inflammatory dysregulation and chronic phase structural remodeling. However, the exact molecular mediators remain unclear. Macrolide antibiotics remain the primary clinical treatment; however, therapeutic limitations persist owing to increasing drug resistance and the lack of immunopathological interventions. In the migration phase, sustained immune activation and abnormal repair processes persist even after pathogen clearance, resulting in chronic lung injury and fibrosis, with underlying immunological mechanisms still poorly understood. This review synthesizes current insights into immune dysregulation across the acute-to-chronic spectrum of MPP, identifies unresolved immunopathological bottlenecks, and highlights translational opportunities for immune-targeted interventions beyond antibiotics.