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Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      The white-footed deermouse\n                      <jats:italic>Peromyscus leucopus<\/jats:italic>\n                      is a primary reservoir for the\nagents of Lyme disease and other zoonoses in North America and manifests infection tolerance for the\nbacteria, protozoa, and viruses it hosts. In previous in vivo studies,\n                      <jats:italic>P. leucopus<\/jats:italic>\n                      and\n                      <jats:italic>Mus musculus<\/jats:italic>\n                      differed in the degree of sickness and profiles of biomarkers after exposure to a bacterial lipopolysaccharide, a TLR4 agonist.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      As an approach for assessing immunity of mammals in nature and for longitudinal studies of colony\nanimals in the laboratory, we evaluated primary dermal fibroblast cultures of\n                      <jats:italic>P. leucopus<\/jats:italic>\n                      and\n                      <jats:italic>M. musculus<\/jats:italic>\n                      in their short-term responses to a TLR2 agonist lipopeptide using bulk and single-cell RNA-seq.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      By single-cell RNA-seq, cultures of both species comprised at least two types of fibroblasts,\nwhich were further differentiated in their responses to TLR agonists. With continued passage, the\nmouse cell population lost viability, while the deermouse cell population spontaneously transformed\ninto a cell line stably maintained under standard conditions. Bulk RNA-seq revealed distinctive\nprofiles for deermouse and mouse cells in arginine metabolism gene expression, high baseline\ntranscription of the antioxidant transcription factor Nfe2l2 (Nrf2) in deermouse fibroblasts, and\nthe transcription of the aging-associated cytokine interleukin-11 in agonist-treated mouse fibroblasts but not deermouse fibroblasts. In the cultures of both species, there was increased transcription of several types of endogenous retrovirus (ERV) and transposable elements (TEs) after exposure to the agonist. The transcribed ERV\/TE sequences in\n                      <jats:italic>M. musculus<\/jats:italic>\n                      cells were generally longer in length and had greater potential for translation than sequences in treated\n                      <jats:italic>P. leucopus<\/jats:italic>\n                      cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The results indicate the feasibility of this in vitro model for both laboratory- and\nfield-based studies, and that inherent differences between deer mice and mice in\ncell-autonomous innate immune responses and ERV\/TE activation can be demonstrated in dermal fibroblasts as well as the animals themselves.<\/jats:p>\n                  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