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Prior efforts have mostly focused on Dipteran insects, which only account for a subset of existing arthropod species in nature. Here we use and develop advanced techniques to describe immune cells (hemocytes) from the clinically relevant tick\n                    <jats:italic>Ixodes scapularis<\/jats:italic>\n                    at a single-cell resolution. We observe molecular alterations in hemocytes upon feeding and infection with either the Lyme disease spirochete\n                    <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                    or the rickettsial agent\n                    <jats:italic>Anaplasma phagocytophilum<\/jats:italic>\n                    . We reveal hemocyte clusters exhibiting defined signatures related to immunity, metabolism, and proliferation. Depletion of phagocytic hemocytes affects\n                    <jats:italic>hemocytin<\/jats:italic>\n                    and\n                    <jats:italic>astakine<\/jats:italic>\n                    levels, two\n                    <jats:italic>I. scapularis<\/jats:italic>\n                    hemocyte markers, impacting blood-feeding, molting behavior, and bacterial acquisition. Mechanistically, astakine alters hemocyte proliferation, whereas hemocytin affects the c-Jun N-terminal kinase (JNK) signaling pathway in\n                    <jats:italic>I. scapularis<\/jats:italic>\n                    . Altogether, we discover a role for tick hemocytes in immunophysiology and provide a valuable resource for comparative biology in arthropods.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-46494-3","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T01:29:47Z","timestamp":1709861387000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Tick hemocytes have a pleiotropic role in microbial infection and arthropod fitness"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1059-3578","authenticated-orcid":false,"given":"Agustin","family":"Rolandelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2267-4634","authenticated-orcid":false,"given":"Hanna J.","family":"Laukaitis-Yousey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haikel N.","family":"Bogale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisha","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0746-3924","authenticated-orcid":false,"given":"Sourabh","family":"Samaddar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anya J.","family":"O\u2019Neal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4550-0773","authenticated-orcid":false,"given":"Camila R.","family":"Ferraz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Butnaru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0172-8090","authenticated-orcid":false,"given":"Enzo","family":"Mameli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baolong","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9508-9372","authenticated-orcid":false,"given":"M. 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