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

TL;DR

This paper reviews how Mycoplasma pneumoniae causes pneumonia by disrupting the immune system, evading defenses, and causing long-term lung damage.

Contribution

The paper provides a comprehensive synthesis of immune dysregulation mechanisms in MPP and identifies translational opportunities for immune-targeted therapies.

Findings

Mycoplasma pneumoniae triggers immune dysregulation through excessive inflammation and immune evasion strategies.

Persistent immune activation after infection leads to chronic lung injury and fibrosis.

Current treatments like macrolides face limitations due to drug resistance and lack of immunopathological interventions.

Abstract

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.

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