Dual RNA-seq reveals the complement protein C3-mediated host-pathogen interaction in the brain abscess caused by Staphylococcus aureus

mSystems, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

ABSTRACT This study aimed to elucidate the complement protein C3-mediated host-pathogen interaction in brain abscess caused by Staphylococcus aureus infection. Dual RNA-seq was employed analyze transcriptomic differences between C3 deficiency and wild-type mice of S. aureus- induced model, then we investigated potential regulatory pathways host mediated genes associated with pathogenesis abscess. Finally, deficient-mice hla mutants were used verify specific pathogen-host interaction. In mouse analysis revealed significant changes bacterial virulence factors, such as hemolysin. Based on these data, predicted a network formed like hrcA dnaK , which represent possible regulation mechanism responding host. Furthermore, identified that response gene . From perspective, observed absence significantly impacted host’s inflammatory response, primarily altering expression several key immune pathways. These findings suggest may impair ability recognize respond external pathogens. To best our knowledge, this proposed affect through C3, plays critical role regulating inflammation signaling IMPORTANCE work, immunofluorescence Western blot reveal upregulation microglia-derived model By integrating individual RNA sequencing data dual infection identified, not only affects but also mediates provided novel targets for therapeutic strategies mitigating effects infections improving treatment outcomes.

Language: Английский

Plasma Exosomal-Derived SERPINA1 and GNAI2 Downregulation as Potential Diagnostic Biomarkers of Kawasaki Disease with Coronary Artery Aneurysms

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2668 - 2668

Published: March 16, 2025

Kawasaki disease (KD) with coronary artery aneurysms (CAAs) is currently the primary cause of childhood acquired heart an unclear pathogenesis. We established five groups for discovery differentially expressed proteins (DEPs): healthy control, febrile KD without CAAs, small and medium giant CAAs (n = 8 in each group). The validation selected DEPs was conducted another 4 comprehensive bioinformatics analyses to elucidate functional roles CAAs. A total 104 were identified patients, which primarily associated complement-related pathways. trend analysis these revealed 54 significantly changed increased severity, G-protein-related functions. alterations α-1-antitrypsin short peptide (SERPINA1) guanine nucleotide-binding protein G(i) subunit alpha-2 (GNAI2), from pathways, respectively, validated by Western blotting, they decreased patients vs. In addition, we separately. There 91 specifically neutrophil extracellular trap complement while 16 specific those viral infection immunity Additionally, among different severities there 102 pathways platelet activation whereas 34 Rap1 signaling pathway cell conclusion, this study provides plasmatic exosomal profiles suggesting that SERPINA1 GNIA2 might serve as novel potential diagnostic biomarkers

Language: Английский

Complement C3/C3aR Signaling Pathway Inhibition Ameliorates Retinal Damage in Experimental Retinal Vein Occlusion

Investigative Ophthalmology & Visual Science, Journal Year: 2025, Volume and Issue: 66(5), P. 2 - 2

Published: May 1, 2025

Retinal vein occlusion (RVO) is a common retinal vascular disease that severely threatens visual function. This study aims to elucidate the role of complement C3/C3aR signaling pathway in laser-induced RVO mouse model and explore its potential as therapeutic target. was induced C57BL/6J mice using laser photocoagulation combined with photosensitizer dye administration. Two days later, tissues were collected for bulk RNA sequencing. The activation validated through RT-qPCR Western blot. C3aR antagonist SB290157 (C3aRA) administered intravitreally morphological functional changes examined 1, 2, 8 later by optical coherence tomography (OCT), fundus photography (FP), fluorescein angiography (FA), optomotor response (OKR) test, electroretinogram (ERG). exhibited marked increases thickness (P < 0.001) fluorescence leakage 0.01) compared sham-laser group. Bulk RNA-seq revealed significant upregulation pathway. Elevated expression C3 0.05) confirmed Blocking significantly alleviated RVO-induced edema, leakage, structural damage. Functional assessment showed treatment improved contrast sensitivity 0.05), increased b-wave 0.001), oscillatory potentials (Ops) amplitudes mice. analysis demonstrated reduced inflammatory mediator-related pathways upregulated perception 0.05). critically involved damage targeting this may be promising approach treatment.

Language: Английский