Transcriptomic analysis of WT and Polg R292C/R292C lungs six hours after intratrachael instillation of Pseudomonas aeruginosa

Mitochondrial diseases (MtD) represent a significant public health challenge due to their heterogenous clinical presentation, often severe and progressive symptoms, and lack of effective therapies. Environmental exposures, such bacterial and viral infection, can further compromise mitochondrial function and exacerbate the progression of MtD. Infections in MtD patients more frequently progress to sepsis, pneumonia, and other detrimental inflammatory endpoints. However, the underlying immune alterations that enhance immunopathology in MtD remain unclear, constituting a key gap in knowledge that complicates treatment and increases mortality in this vulnerable population. This dataset reports transcriptomic changes in lungs from wild-type mice and a mouse model of polymerase gamma (Polg)-related MtD (Polg R292C/R292C) six hours post intratrachael instillation of Pseudomonas aeruginosa strain PAO1. These data reveal a hyperinflammatory innate immune status in Polg R292C lungs characterized by elevated expression of genes involved in interferon and inflammatory cell death pathways. This work sheds new light on innate immune dysregulation in a model of mitochondrial dysfunction and reveals potential targets for limiting infection- and inflammation-related complications in Polg-related MtD. WT and Polg R292C/R292C mice (3 males per genotype, 3 months old) on a C57BL/6N background were challenged with 1x10^6 GFP-tagged Pseudomonas aeruginosa strain PAO1 by intratrachael instillation under anesthesia. 6 hours post instillation, mice were sacraficed and lungs were isolated and snap frozen in liquid nitrogen. Frozen lung tissue was crushed into powder in liquid nitrogen, then total RNA was extracted using a Direct-Zol RNA miniprep kit (Zymo Research). Stranded libraries were constructed by the Genome Technologies Scientific Service at The Jackson Laboratory using the KAPA mRNA HyperPrep Kit (Roche Sequencing and Life Science according to the manufacturer’s protocol. Libraries were then sequenced 150bp paired-end on an Illumina NovaSeq X Plus using the 10B Reagent kit. FASTQ files were imported into Partek Flow software (build 12.5.0, Illumina), reads were aligned with STAR Aligner 2.7.8a, then filtered and normalized into the assembeled count file.