Role of the Notch ligand DLL4 in the immune response of children with Mycoplasma pneumoniae pneumonia

Authors

  • Heting Dong Soochow University, Children’s Hospital, Department of Respiratory Medicine, Suzhou, China
  • Zhiao Du Soochow University, Children’s Hospital, Department of Respiratory Medicine, Suzhou, China
  • Yaru Liao Shandong University, Children’s Hospital, Department of Respiratory Medicine, Jinan, China
  • Jiying Sun Soochow University, Children’s Hospital, Department of Respiratory Medicine, Suzhou, China
  • Huiming Sun Soochow University, Children’s Hospital, Department of Respiratory Medicine, Suzhou, China
  • Peng Mo Soochow University, Children’s Hospital, Department of Respiratory Medicine, Suzhou, China
  • Ge Dai Soochow University, Children’s Hospital, Department of Respiratory Medicine, Suzhou, China
  • Li Huang Soochow University, Children’s Hospital, Department of Respiratory Medicine, Suzhou, China
  • Feng Huang Soochow University, Children’s Hospital, Department of Respiratory Medicine, Suzhou, China
  • Chuangli Hao Soochow University, Children’s Hospital, Department of Respiratory Medicine, Suzhou, China
  • Zhengrong Chen Soochow University, Children’s Hospital, Department of Respiratory Medicine, Suzhou, China
  • Yongdong Yan Soochow University, Children’s Hospital, Department of Respiratory Medicine, Suzhou, China https://orcid.org/0009-0004-1083-9587

DOI:

https://doi.org/10.1590/S1678-9946202567065

Keywords:

Mycoplasma pneumoniae, Pneumonia, Notch, DLL4, Cytokines, Lymphocyte subsets

Abstract

Mycoplasma pneumoniae pneumonia (MPP) is a common pediatric respiratory infection linked to excessive immune-inflammatory responses. This study investigated the role of the Notch ligand DLL4 in the immunopathogenesis of MPP by assessing its expression in peripheral blood mononuclear cells of affected children. A total of 128 children with MPP and 35 controls were recruited. PBMCs were analyzed for the expression of Notch ligands (Jagged1, Jagged2, DLL1, DLL4) using real-time PCR. Lymphocyte subsets were assessed via flow cytometry, and cytokine levels were measured using ELISA. Clinical data were compared between severe and mild MPP cases, and correlations between DLL4 expression and immune indicators were evaluated. DLL4 expression was significantly higher in the MPP and severe MPP groups than in controls (P < 0.01). MPP patients showed lower CD3+ and CD3+CD4+ lymphocyte levels, and higher CD3+CD8+ and CD3-CD19+ levels compared with controls (P < 0.001). Plasma levels of IFN-γ, IL-17, and IL-36α were elevated in MPP patients (P < 0.001), whereas IL-4 and IL-10 levels were reduced (P < 0.01). Severe cases had higher IFN-γ, IL-17, and IL-36α levels than mild cases (P < 0.05). DLL4 expression positively correlated with plasma IFN-γ and IL-17 levels in MPP patients (P < 0.05). Elevated DLL4 expression in MPP patients, particularly in severe cases, suggests its role in enhancing Th1/Th17-mediated immune responses while suppressing Th2 pathways. Such findings implicate the Notch signaling pathway, via DLL4, in the immunopathogenesis of MPP and highlight its potential as a therapeutic target for modulating immune responses in severe MPP.

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Published

2025-10-20

Issue

Section

Original Article

How to Cite

Dong, H., Du, Z., Liao, Y., Sun, J., Sun, H., Mo, P., Dai, G., Huang, L., Huang, F., Hao, C., Chen, Z., & Yan, Y. (2025). Role of the Notch ligand DLL4 in the immune response of children with Mycoplasma pneumoniae pneumonia. Revista Do Instituto De Medicina Tropical De São Paulo, 67, e65. https://doi.org/10.1590/S1678-9946202567065