Animals that are competent reservoirs of zoonotic pathogens commonly suffer little morbidity or apparent pathology from the infections. To investigate mechanisms of this tolerance of infection, we used single-dose lipopolysaccharide (LPS) as an experimental model of inflammation and compared the four hour post-injection responses by three rodents: the cricetine rodent Peromyscus leucopus (LL stock), the white-footed deermouse and reservoir for agents of Lyme disease and other zoonoses, and the murids Mus musculus (outbred CD-1 breed), the house mouse, and Rattus norvegicus, the brown rat (Fischer strain). The data presented here are part of a follow-up study of this phenomenon that was previoiusly reported with the title "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). The manuscript associated with the accompanying data of this follow-up study is in preparation. The basic experimental design (described below) is the same as for the prior study: a genome-wide RNA-seq of whole blood using reference transcript set and then an analysis for differential gene expression (DEG) between LPS-treated animals and controls for each of the species. The accompanying dataset comprises the DEGs for deermice, mice, and rats in this study. There were multiple differences in the rankings of the DEGs by lowest p value between species with the greatest number of differences between P. leucopus, which is in the familly Cricetidae, and the mice and rats, which are in the family Muridae. Overall, the deermice in the study displayed a greater anti-inflammatory response than the mice and rats in the study. An example was interferon-gamma (Ifng) which was one of the top ranked DEGs for the mice and rats but not for the deermice.

Adult animals of the species Peromyscus leuopus LL stock, Mus musculus (CD-1 breed) or Rattus norvegicus Fischer strain were inoculated into the peritoneum (IP) with solution of purified E. coli lipopolysaccharide (10 microgram/gram body mass for P. leuocpus and M. musculus and 5 microgram or 20 microgram for R. norvegicus. Controls received saline alone. P. leucopus and M. musculus were in the same experiment and there were 10 animals (5 of each sex) in the treatment group and 10 animals (5 of each sex) in the control group. The rats were studied in a separate experiment with 5 control animals and 6 animals receiving 5 microgram LPS per gram and 5 animals receiving 20 micrograms LPS per gram. In both experiments 4 hours after LPS or control injections the animals were humanely euthanized and blood collected for complete blood count and for RNA extraction. The extracte RNA was subjected to stranded cDNA library preparation and then Illumina technology (Novaseq) as described in https://doi.org/10.1128/mBio.00588-21 with paired-end sequencing chemistry and 150 cycles for the deermouse and mouse samples and 100 cycles for the rat samples. There were an average of ~50 million reads per sample. After quality control and trimming the reads were matched to current genome-wide transcript sets for reference genomes for P. leucopus. M. musculus, and R. norvegicus using CLC Genomics Workbench v. 23. Differential gene expression (DEG) was assessed using the same suite of software and a modification of EdgeR method. The genes listed in the table had false discovery rate p values of less than 0.05 and fold-changes up or down of greater than 1.5X.

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