Knocking down ABCG1 activates NLRP3/Caspase-1 pathway to promote neutrophil pyroptosis and exacerbate Mycoplasma pneumoniae pneumonia in children​Lisha Cai on 13 de November de 2025 at 11:00

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J Leukoc Biol. 2025 Nov 13:qiaf163. doi: 10.1093/jleuko/qiaf163. Online ahead of print.

ABSTRACT

Mycoplasma pneumoniae (Mp) is a frequent cause of pediatric pneumonia, largely due to the challenges in early detection and the tendency to underestimate the severity of infections. Emerging evidence suggests that ATP-binding cassette transporter G1 (ABCG1) plays a critical role in preventing lung inflammation. Our study investigates the connection between ABCG1 and Mycoplasma pneumoniae pneumonia (MPP) and explores the mechanisms involved, with the goal of providing a theoretical basis for the clinical diagnosis of MPP in children. The influence of Mp infection on ABCG1 expression levels in murine neutrophil cell line (MNHC) was examined, followed by a combination of shRNA interference, quantitative reverse transcription polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay to explore the role of ABCG1 in Mp-induced pyroptosis of neutrophils. Additionally, we explored the clinical correlation between ABCG1 expression and NLRP3 inflammasome activation in children with MPP. Mp infection led to decreased ABCG1 expression in murine neutrophils, which in turn boosted NLRP3 levels. The elevated NLRP3 activated the Caspase-1/GSDMD pathway, driving neutrophil pyroptosis and the release of IL-1β and IL-18. These events aggravated theinflammatory response induced by Mp infection. Our clinical data also indicated a significant negative correlation between the mRNA expression of ABCG1 and NLRP3 in peripheral blood and neutrophils of children with MPP. ABCG1 can mitigate pediatric MPP by regulating the NLRP3/Caspase-1 pathway to inhibit neutrophil pyroptosis. This mechanism indicates that ABCG1 could be a valuable biomarker for pediatric MPP, with significant implications for clinical management.

PMID:41229317 | DOI:10.1093/jleuko/qiaf163

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