Abstract
Background
The underlying mechanisms for infantile bronchopneumonia development remain unknown.
Methods
Peripheral blood mononuclear cell (PBMCs) and serum derived from severe and mild infantile bronchopneumonia were obtained, and the expression of various molecules was detected with enzyme-linked immunosorbent assay and quantitative PCR. Such molecules were also detected in granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced bone marrow-derived NFκB2−/− dendritic cells (DCs) or NIK SMI1 (NF-κB-inducing kinase inhibitor) administrated DCs.
Results
The relative mRNA expression levels of type I interferons (IFNs) (IFN-α4, IFN-β), Th17 cell-associated markers (interleukin-17A, retinoic-acid-receptor-related orphan nuclear receptor gamma, and GM-CSF), and non-canonical NF-κB member (NFκB2) were significantly up-regulated in PBMCs and DCs derived from infantile bronchopneumonia compared with healthy controls. However, compared with Th17 cell-associated markers and non-canonical NF-κB molecules, the expression of IFN-α4 and IFN-β was significantly inhibited in severe infantile bronchopneumonia compared with mild infantile bronchopneumonia. The relative protein expression of the above molecules also showed a similar expression pattern in the PBMCs or serum. NF-κB2 knockout or NIK SMI1 administration could reverse the diminished expression of IFN-β in GM-CSF-induced bone marrow-derived DCs.
Conclusions
GM-CSF-dependent non-canonical NF-κB pathway-mediated inhibition of type I IFNs production in DCs contributes to the development of severe bronchopneumonia in infant.
Impact
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Granulocyte-macrophage colony-stimulating factor-dependent non-canonical NF-κB pathway-mediated inhibition of type I IFNs production in dendritic cells is critical for the development of infantile bronchopneumonia.
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Our findings reveal a possible mechanism underlying the development of severe infantile bronchopneumonia.
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The results could provide therapeutic molecular target for the treatment of such disease.
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Data availability
Data could be obtained upon reasonable request to the corresponding author.
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L.X. designed and supervised the study. Z.L. and H.W. performed experiments and analyzed data. Z.L. wrote and revised the manuscript. All authors reviewed the results and approved the final version of the manuscript.
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Protocol of this research was approved by the Ethics Committee of Daqing Oilfield General Hospital.
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Luo, Z., Wei, H. & Li, X. Granulocyte-macrophage colony-stimulating factor suppresses induction of type I interferon in infants with severe pneumonia. Pediatr Res 93, 72–77 (2023). https://doi.org/10.1038/s41390-022-02059-y
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DOI: https://doi.org/10.1038/s41390-022-02059-y
