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Updated: Jul 3, 2025
Histological Quantification to Determine Lung Fungal Burden in Experimental Aspergillosis
Published on: March 9, 2018
Identifying genetic susceptibility to Aspergillus fumigatus infection using collaborative cross mice and RNA-Seq
Roa'a H S Yosief1, Iqbal M Lone1, Aharon Nachshon2
1Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Background:
Aspergillus fumigatus (Af) is one of the most ubiquitous fungi and its infection potency is suggested to be strongly controlled by the host genetic background. The aim of this study was to search for candidate genes associated with host susceptibility to Aspergillus fumigatus (Af) using an RNAseq approach in CC lines and hepatic gene expression.
Methods:
We studied 31 male mice from 25 CC lines at 8 weeks old; the mice were infected with Af. Liver tissues were extracted from these mice 5 days post-infection, and next-generation RNA-sequencing (RNAseq) was performed. The GENE-E analysis platform was used to generate a clustered heat map matrix.
Results:
Significant variation in body weight changes between CC lines was observed. Hepatic gene expression revealed 12 top prioritized candidate genes differentially expressed in resistant versus susceptible mice based on body weight changes. Interestingly, three candidate genes are located within genomic intervals of the previously mapped quantitative trait loci (QTL), including Gm16270 and Stox1 on chromosome 10 and Gm11033 on chromosome 8.
Conclusions:
Our findings emphasize the CC mouse model's power in fine mapping the genetic components underlying susceptibility towards Af. As a next step, eQTL analysis will be performed for our RNA-Seq data. Suggested candidate genes from our study will be further assessed with a human cohort with aspergillosis.
Insights
This study identifies 12 candidate genes linked to host susceptibility in Aspergillus fumigatus (Af) infections using RNA sequencing in mouse models. These findings advance understanding of Af infection genetics and potential therapeutic targets.
Area of Science:
- Genomics
- Infectious Disease Research
- Host-Pathogen Interactions
Background:
- Aspergillus fumigatus (Af) is a widespread fungus, with host genetics significantly influencing infection severity.
- Identifying genetic factors controlling Af susceptibility is crucial for understanding disease outcomes.
Purpose of the Study:
- To identify candidate genes associated with host susceptibility to Aspergillus fumigatus (Af) infections.
- To leverage RNA sequencing (RNAseq) in a mouse model to pinpoint genetic determinants of Af infection response.
Main Methods:
- RNA sequencing was performed on liver tissues from 31 male mice across 25 Collaborative Cross (CC) lines post-Af infection.
- Gene expression data was analyzed to identify differentially expressed genes between resistant and susceptible mice, categorized by body weight changes.
- A clustered heatmap matrix was generated using the GENE-E analysis platform.
Main Results:
- Significant variations in body weight changes were observed among different CC mouse lines, indicating differential susceptibility.
- Twelve top candidate genes were identified through hepatic gene expression analysis, showing differential expression in resistant versus susceptible mice.
- Three candidate genes (Gm16270, Stox1, Gm11033) were found within previously mapped quantitative trait loci (QTL) regions.
Conclusions:
- The CC mouse model is effective for fine-mapping genetic components of Af susceptibility.
- Further analysis, including eQTL analysis, is planned for the RNA-Seq data.
- Candidate genes identified will be evaluated in a human cohort with aspergillosis to assess clinical relevance.
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