Ferroptosis Key Genes and Immune Infiltration in Legionnaires' Disease: Bioinformatics and Animal Model Evidence.
TL;DR
This study confirms ferroptosis plays a critical role in Legionnaires' disease pathogenesis, and the 7 core genes provide novel insights into the molecular mechanisms of the disease.
Abstract
Background
Legionnaires' disease (LD) primarily presents with fever and pneumonia. Legionella pneumophila (L. pneumophila), a facultative intracellular pathogen capable of forming structured biofilms, poses two well-recognized clinical challenges for Legionnaires' disease treatment: antibiotic resistance and the difficulty of eradicating persistent intracellular infections. Ferroptosis, an iron-dependent regulated cell death modality, is implicated in the pathogenesis of diverse bacterial infections, but its specific regulatory mechanism in L. pneumophila infection remains largely uncharacterized. This study aims to identify key ferroptosis-related genes during L. pneumophila infection via bioinformatics analysis and molecular biological validation, to provide theoretical support for subsequent research.
Methods
Transcriptomic datasets of L. pneumophila infection models were retrieved from the Gene Expression Omnibus. Differentially expressed genes were screened, intersected with curated Ferroptosis Database, and validated in independent mouse infection cohorts. Candidate genes were characterized via protein-protein interaction network analysis, functional enrichment analysis, immune infiltration correlation analysis, and quantitative real-time polymerase chain reaction validation.
Results
A total of 23 ferroptosis-associated shared differentially expressed genes were identified, with 7 core candidates (Cav1, Hif1α, Hspa1b, Stat3, CD44, Cxcl10, Ptgs2) showing consistent statistically significant differential expression across validation cohorts and experimental assays. These core genes act via independent regulatory pathways, suggesting ferroptosis is triggered by multiple mechanisms during infection, and mediate activation of multiple immune cell subsets.
Conclusions
This study confirms ferroptosis plays a critical role in Legionnaires' disease pathogenesis, and the 7 core genes provide novel insights into the molecular mechanisms of the disease.