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The ability for these ticks to survive in nature is credited, in part, to their ability to feed on a variety of hosts without triggering an immune response capable of preventing tick feeding. While the ability of nymphal ticks to feed on a variety of hosts has been well documented, the host-parasite interactions between larval\n                      <jats:italic>I. scapularis<\/jats:italic>\n                      and different vertebrate hosts are relatively unexplored. Here we report on the changes in the vertebrate host transcriptome present at the larval tick bite site using the natural\n                      <jats:italic>I. scapularis<\/jats:italic>\n                      host\n                      <jats:italic>Peromyscus leucopus<\/jats:italic>\n                      , a non-natural rodent host,\n                      <jats:italic>Mus musculus<\/jats:italic>\n                      (BALB\/c), and humans. We note substantially less evidence of activation of canonical proinflammatory pathways in\n                      <jats:italic>P. leucopus<\/jats:italic>\n                      compared to BALB\/c mice and pronounced evidence of inflammation in humans. Pathway enrichment analyses revealed a particularly strong signature of interferon gamma, tumor necrosis factor, and interleukin 1 signaling at the BALB\/c and human tick bite sites. We also note that bite sites on BALB\/c mice and humans, but not deer mice, show activation of wound-healing pathways. These data provide molecular evidence of the coevolution between larval\n                      <jats:italic>I. scapularis<\/jats:italic>\n                      and\n                      <jats:italic>P. leucopus<\/jats:italic>\n                      and, in addition, expand our overall understanding of\n                      <jats:italic>I. scapularis<\/jats:italic>\n                      feeding.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00065-25","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T09:02:49Z","timestamp":1741683769000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["<i>Peromyscus leucopus<\/i>\n                    ,\n                    <i>Mus musculus<\/i>\n                    , and humans have distinct transcriptomic responses to larval\n                    <i>Ixodes scapularis<\/i>\n                    bites"],"prefix":"10.1128","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9037-8418","authenticated-orcid":true,"given":"Jeffrey S.","family":"Bourgeois","sequence":"first","affiliation":[{"name":"Tufts Lyme Disease Initiative, Department of Molecular Biology and Microbiology, Tufts University School of Medicine","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie E.","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Tufts Lyme Disease Initiative, Department of Molecular Biology and Microbiology, Tufts University School of Medicine","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siu-Ping","family":"Turk","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), NIH","place":["Bethesda, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie S.","family":"You","sequence":"additional","affiliation":[{"name":"Tufts Lyme Disease Initiative, Department of Molecular Biology and Microbiology, Tufts University School of Medicine","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quentin","family":"Bernard","sequence":"additional","affiliation":[{"name":"Tufts Lyme Disease Initiative, Department of Molecular Biology and Microbiology, Tufts University School of Medicine","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke H.","family":"Clendenen","sequence":"additional","affiliation":[{"name":"Tufts Lyme Disease Initiative, Department of Molecular Biology and Microbiology, Tufts University School of Medicine","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8743-0948","authenticated-orcid":true,"given":"Gary 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