Differentially-expressed genes in blood in response to lipopolysaccharide in three rodent species

Infection tolerance in rodents was examined by injecting single-dose lipopolysaccharide (LPS) to induce inflammation in Peromyscus leucopus (LL stock), the white-footed deermouse also reservoir for Lyme disease and Mus musculus (outbred CD-1 breed), the house mouse, and Rattus norvegicus, the brown rat (Fischer strain). Reaction to LPS was analyzed in the blood of challenged rodents and compared to control animals. As natural reservoirs of zoonoses deermice show significant anti-inflammatory response as described in "An Infection-Tolerant Mammalian Reservoir for Several Zoonotic Agents Broadly Counters the Inflammatory Effects of Endotoxin" (https://doi.org/10.1128/mBio.00588-21). The project and the description of the samples are described under the following NCBI BioProjects: PRJNA975149 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA975149) for mouse and deermouse and PRJNA973677 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA973677). This project is a follow-up project focusing on the transcriptomic analysis of the whole blood bulk RNA-seq and further analysis of differentially expressed genes (DEG) between the treatment arm and controls. Complete fold change and false discovery rate for all three rodent species used for the current Dryad set are previously published (https://doi.org/10.7280/D1470Z). Here we report that deermice tolerance to infection is partly due to lower expression of interferon-gamma in comparison to mice and rats. 

Methods
Peromyscus leucopus (10 animals, 5 of each sex) and M. musculus (10 animals, 5 of each sex) were injected into the peritoneum with the solution of purified E. coli lipopolysaccharide (10 microgram/gram of body weight). Same number of animals was injected with saline and used as controls. The rats were studied in a separate experiment with 5 control animals and 6 animals receiving 5 micrograms LPS per gram of body weight and 5 animals receiving 20 micrograms LPS per gram. All animals were euthanized 4 hours post-injection. Blood from each animal was used for extracting RNA and processed further using Novaseq Illumina technology with paired-end chemistry and 150 cycles for mice and deermice and 100 cycles for rats providing ~ 50 million reads per sample. After sequencing reads were trimmed and transcripts annotated using Genomics Workbench v. 23. Differential gene expression (DEG) was assessed using the same suite of software and a modification of EdgeR method. Sequenced data was deposited to National Center for Biotechnology Information (https://ncbi.nlm.nih.gov) BioProjects PRJNA975149 for the combined P. leucopus and M. musculus experiment (SRX20511260-SRX20511299), and PRJNA973677 for the R. norvegicus LPS experiment (SRX20509401-SRX20509416).