Identifying genetic susceptibility to Aspergillus fumigatus infection using collaborative cross mice and RNA-Seq approach

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 back-ground.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 ob-served.Hepatic gene expression revealed 12 top prioritized candidate genes differ-entially expressed in resistant versus susceptible mice based on body weight changes.Interestingly,three candidate genes are located within genomic intervals of the previ-ously mapped quantitative trait loci(QTL),including Gm16270 and Stox1 on chromo-some 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.

Renal aspergillosis after liver transplantation: Clinical and imaging manifestations in two cases

Renal aspergillosis(RAsp)is a rare complication in liver transplant(LT)recipients.Here we report RAsp in two LT recipients.In both patients,RAsp occurred more than 90 d after allogenetic orthotropic LT,and all the clinical findings were unspecific.RAsp involved unilateral kidney in Case one and bilateral kidneys in Case two.Both computed tomography(CT)and magnetic resonance imaging(MRI)revealed renal abscesses,with progressively enhanced walls and separationsand unenhanced alveolate areas after contrast agent administration.On unenhanced CT images they showed inhomogeneous hypo-attenuation.On fat-suppressed T2-weighted images(T2WIs),the walls and separations of the abscesses showed slightly low signal intensity and the central parts of the lesions showed slightly high signal intensity.Both on CT and MRI,there were some hints of renal infarction or chronic ischemia.Both cases were treated by radical nephrectomy followed by adjuvant antifungal treatment.They all recovered well.