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Published on: January 7, 2019
Melatonin attenuates Mycoplasma pneumoniae-Induced Inflammation and barrier dysfunction by CXCL10/TLR4/STAT1 axis
Chun-Yi Lee1,2,3, Tsung-Hua Wu2,4, Meei-Ling Sheu5,6,7
1Department of Pediatrics, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan.
Abstract:
Mycoplasma pneumoniae (Mp) is a major pathogen of community-acquired pneumonia increasingly resistant to macrolides. Mp infection provokes oxidative stress, disrupts epithelial integrity, and skews T helper (Th) cell balance through CARDS toxin-mediated immune dysregulation. Here, we investigated the protective effects of melatonin, a pleiotropic hormone with antioxidant and immunomodulatory functions, in patients and a murine model of Mp pneumonia. Mp infection perturbed the local Th1/Th2/Th17 balance, accompanied by ROS accumulation, CXCL10-induced TLR4/STAT1 activation, and loss of ZO1-dependent tight junctions. Melatonin administration suppressed ROS production, restored epithelial barrier integrity, and rebalanced Th responses within the airway microenvironment. Mechanistically, melatonin inhibited CXCL10-TLR4/STAT1 signaling, with TLR4 residue A366 identified as a key regulatory site. These findings reveal that melatonin alleviates Mp-induced airway injury by maintaining immune and epithelial homeostasis, highlighting its potential as an adjunctive therapy for macrolide-resistant Mp pneumonia.
Insights
Melatonin protects against Mycoplasma pneumoniae pneumonia by reducing oxidative stress and restoring immune balance. This suggests melatonin as a potential therapy for macrolide-resistant infections.
Area of Science:
- Immunology
- Pulmonology
- Pharmacology
Background:
- Mycoplasma pneumoniae (Mp) causes community-acquired pneumonia and exhibits increasing macrolide resistance.
- Mp infection induces oxidative stress, damages epithelial barriers, and dysregulates T helper (Th) cell balance via CARDS toxin.
- Melatonin possesses antioxidant and immunomodulatory properties.
Purpose of the Study:
- To investigate the protective effects of melatonin against Mp-induced pneumonia in patients and a murine model.
- To elucidate the underlying mechanisms of melatonin's action in mitigating Mp-induced airway injury.
Main Methods:
- Assessment of Mp-induced changes in Th cell balance, reactive oxygen species (ROS) levels, CXCL10-TLR4/STAT1 signaling, and tight junction protein ZO1 expression.
- Administration of melatonin to Mp-infected patients and mice.
- Identification of key regulatory sites in TLR4 signaling.
Main Results:
- Mp infection disrupted Th1/Th2/Th17 balance, increased ROS, activated CXCL10-TLR4/STAT1 signaling, and compromised epithelial ZO1 integrity.
- Melatonin treatment suppressed ROS production, restored epithelial barrier function, and rebalanced Th cell responses.
- Melatonin inhibited CXCL10-TLR4/STAT1 signaling, with TLR4 residue A366 identified as critical.
Conclusions:
- Melatonin alleviates Mp-induced airway injury by preserving immune and epithelial homeostasis.
- Melatonin demonstrates potential as an adjunctive therapy for macrolide-resistant Mycoplasma pneumoniae pneumonia.
