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STAT2-IRF1-ISG15-Associated Temporal Immune Reprogramming in Macrophages during Aspergillus fumigatus Infection
Quan Zhou1,2, Rendong Li3, Dandan Song1,2
1Department of Dermatology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Current Microbiology
|June 20, 2026
Summary
This study reveals how macrophages transition their immune response to Aspergillus fumigatus, identifying a STAT2-IRF1-ISG15 pathway crucial for antifungal defense in immunocompromised individuals.
Area of Science:
- Immunology
- Molecular Biology
- Bioinformatics
Background:
- Invasive aspergillosis by Aspergillus fumigatus is a severe threat to immunocompromised individuals, with high mortality.
- Macrophages initiate early defense against A. fumigatus, but the dynamics of their immune reprogramming are not fully understood.
Purpose of the Study:
- To characterize the temporal immune reprogramming of macrophages upon exposure to A. fumigatus.
- To identify key regulatory modules and signaling pathways involved in macrophage antifungal defense.
Main Methods:
- Time-series transcriptomics of human monocyte-derived macrophages exposed to A. fumigatus conidia (0-8 hours).
- Bioinformatics analyses including gene set enrichment analysis (GSEA) and temporal clustering.
- Experimental validation using qRT-PCR and Western blotting in THP-1 derived macrophages.
Main Results:
- Gene expression progressively increased, peaking at 8 hours with thousands of upregulated and downregulated genes.
- Early TNF-α/NF-κB signaling was followed by a prominent interferon-γ response at 8 hours.
- A STAT2-IRF1-ISG15 transcriptional program was identified, with sequential protein induction and phosphorylation.
Conclusions:
- The study elucidates a STAT2-IRF1-ISG15 associated transcriptional program in macrophages during A. fumigatus challenge.
- This program may mediate the shift from an initial inflammatory response to an interferon-augmented defense.
- Findings provide insights into macrophage immune reprogramming critical for combating invasive aspergillosis.
