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High-Throughput Transcriptome Analysis for Investigating Host-Pathogen Interactions
Published on: March 5, 2022
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Transcriptional profiling specifies the pathogen-specific human host response to infectious keratitis
Thabo Lapp1,2, Paola Kammrath Betancor1, Günther Schlunck1
1Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.
Frontiers in Cellular and Infection Microbiology
|January 26, 2024
Summary
High-resolution transcriptomic profiling reveals distinct molecular mechanisms in human corneal infections. This study differentiates viral and bacterial/fungal keratitis, offering insights for new diagnostics and therapies to combat vision loss.
Area of Science:
- Ophthalmology
- Molecular Biology
- Immunology
Background:
- Corneal infections are a significant cause of visual impairment and blindness globally.
- Understanding the molecular basis of host response is crucial for effective treatment.
Purpose of the Study:
- To apply high-resolution transcriptomic profiling to elucidate molecular and cellular mechanisms in human corneal infections.
- To differentiate host responses to viral (herpes simplex virus) versus bacterial/fungal keratitis.
Main Methods:
- Analysis of formalin-fixed, paraffin-embedded (FFPE) human corneal specimens using Massive Analysis of cDNA Ends (MACE RNA-seq).
- Bioinformatic deconvolution (xCell, CYBERSORTx) and integration with single-cell RNA-seq data to investigate cellular host response.
Main Results:
- Identified 216 and 561 overexpressed genes specific to viral and bacterial/fungal keratitis, respectively.
- Viral keratitis response driven by adaptive immunity; bacterial/fungal response by innate immunity.
- Key genes/pathways identified: CXCL9, CXCR3, MMP9 (viral); S100A8/A9, MMP9, IL17 pathway (bacterial/fungal).
Conclusions:
- High-resolution molecular profiling offers novel insights into human corneal host responses to infection.
- Pathogen-specific profiles can inform development of diagnostic biomarkers and targeted therapies.
- Aims to reduce inflammation-induced damage and improve outcomes for infectious keratitis.
