DOI: 10.7280/d12m4n
title: Untargeted metabolomics molecular features data for plasma of 20 Peromyscus leucopus and 20 Mus musculus treated with LPS or controls

description: Animals that are competent natural reservoirs of zoonotic diseases
 commonly suffer little morbidity from the pathogens they persistently
 harbor. The mechanisms of this infection tolerance and the trade-off costs
 are poorly understood. We used exposure to a single dose of
 lipopolysaccharide (LPS) endotoxin as an experimental model of
 inflammation to compare the responses of the cricentine rodent Peromyscus
 leucopus, the white-footed deermouse, to that of Mus musculus, the
 standard laboratory model for pathogenesis studies. Four hours after
 injection with either LPS or saline, blood and spleen and liver tissues
 were collected postmortem and subjected to RNA-seq, untargeted
 metabolomics, and specific RT-qPCR. This was followed by analysis of
 differential expression at the gene, pathway, and empirical network
 levels. The deermice showed the same signs of sickness as the mice with
 LPS exposure, and in addition demonstrated comparable increases in levels
 of corticosterone and expression of interleukin (IL)-6, tumor necrosis
 factor, IL-1b, and acute phase reactants, including C-reactive protein.
 But whereas the M. musculus response to LPS was best-characterized by
 network analysis as cytokine-associated, the P. leucopus response was
 dominated by pathway terms associated with neutrophil activity.
 Dichotomies between the species in expression profiles of arginase 1 and
 nitric oxide synthase 2, as well as the ratios of IL-10 to IL-12, were
 consistent with a type M1 polarized macrophage response in the mice and a
 type M2 or alternatively-activated response in the deermice. Analysis of
 metabolites in the plasma and RNA in the tissues revealed differences
 between the two species in tryptophan metabolism during response to LPS.
 Two up-regulated genes in particular signified the difference between the
 species: Slpi (secretory leukocyte proteinase inhibitor) and Ibsp
 (integrin-binding protein sialoprotein). The latter was previously
 unrecognized in the context of inflammation or infection. Key RNA-seq
 findings in P. leucopus were replicated in a second LPS experiment with
 older animals, in a systemic bacterial infection model, and with
 cultivated fibroblasts. Taken together, the results indicate that the
 deermouse possesses several adaptive traits to moderate effects of
 inflammation and oxidative stress ensuing from infection. This seems to be
 at the cost of infection persistence and that is to the benefit of the
 pathogen.  
description: Plasma samples were collected from 20 Peromyscus leucopus and 20
 Mus musculus (BALB/c strain) 4 hours after intraperitoneal injection with
 E. coli lipopolysaccharide at 10 micrograms/gm body weight (12 of each
 species) or with normal saline alone (8 of each species). The animals of
 each species were equally divided by sex.  Forty microliter volumes of
 plasma were extracted with 120 microliters methanol containing as internal
 standards phenylalanine d5 (175 ng/mL), 1-methyl tryptophan (37.5 ng/mL),
 and arachnidonoyl amide (30 ng/mL). After precipitated proteins were
 removed by centrifugation, the supernatant was dried under vacuum and then
 suspended in 50% methanol. Aliquots of 10 microliter were subjected to
 high pressure liquid chromatography (HPLC) and quadrupole (Q)
 time-of-flight (TOF) mass spectrometry (MS) with periodic inclusion of
 pooled samples for quality control. Metabolites were separated on an
 Agilent Technologies Poroshell C8 column (100 x 2.1 mm, 2.7 micron) with a
 gradient of acetonitrile and water both containing 0.1% formic acid with
 an Agilent 1260 HPLC pump. The eluent was introduced into an Agilent
 Technologies 6520 Q-TOF-MS instrument equipped with an electrospray
 ionization source. The parameters for the analysis were a capillary
 voltage of 4000 V, fragmenter voltage of 120 V, gas at 310° C, gas flow of
 10 L/min, and nebulizer pressure of 45 psig. Data were acquired in the
 positive ion mode at a scan range of 75-1700 for the mass-to-charge ratio
 (m/z) and at a rate of 1.67 spectra per second. The raw data files were
 converted to the XML-based mzML format with Proteowizard. The files were
 then processed for peak picking, grouping, and retention time correction
 with the XCMS suite of software. The centWave algorithm was applied to
 detect chromatographic peaks with these parameter settings: ≤ 30 ppm for
 m/z deviation in consecutive peaks, signal to noise ratio of 10, a
 prefilter of 3 scans with peak intensity of ≥ 750, and 10 to 45 s for peak
 width. Molecular features (MF), defined by m/z and retention time, were
 grouped across samples using a bandwidth of 15 and overlapping m/z slice
 of 0.02. Retention time correction was performed with the retcor algorithm
 of XCMS. 
description: The dataset consists of an Excel workbook with two sheets. The
 first sheet contains the data for P. leucopus and the second sheet
 contains the data for M. musculus. The fold change values are for the
 LPS-treated to the control values.  Included on each are the quality
 control (QC) values for each run.