Untargeted metabolomics molecular features data for plasma of 20 Peromyscus leucopus and 20 Mus musculus treated with LPS or controls

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.