{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:44:44Z","timestamp":1781106284736,"version":"3.54.1"},"reference-count":54,"publisher":"National Academy of Sciences","issue":"47","license":[{"start":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070444"],"award-info":[{"award-number":["32070444"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31900331"],"award-info":[{"award-number":["31900331"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,11,22]]},"abstract":"<jats:p>\n                    Lyme spirochetes have coevolved with ticks to optimize transmission to hosts using tick salivary molecules (TSMs) to counteract host defenses. TSMs modulate various molecular events at the tick\u2013host interface. Lymphotoxin-beta receptor (LT\u03b2R) is a vital immune receptor and plays protective roles in host immunity against microbial infections. We found that\n                    <jats:italic>Ltbr<\/jats:italic>\n                    knockout mice were more susceptible to Lyme disease spirochetes, suggesting the involvement of LT\u03b2R signaling in tick-borne\n                    <jats:italic>Borrelia<\/jats:italic>\n                    infection. Further investigation showed that a 15-kDa TSM protein from\n                    <jats:italic>Ixodes persulcatus<\/jats:italic>\n                    (\n                    <jats:italic>I. persulcatus<\/jats:italic>\n                    salivary protein; IpSAP) functioned as an immunosuppressant to facilitate the transmission and infection of Lyme disease spirochetes. IpSAP directly interacts with LT\u03b2R to block its activation, thus inhibiting the downstream signaling and consequently suppressing immunity. IpSAP immunization provided mice with significant protection against\n                    <jats:italic>I. persulcatus\u2013<\/jats:italic>\n                    mediated\n                    <jats:italic>Borrelia garinii<\/jats:italic>\n                    infection. Notably, the immunization showed considerable cross-protection against other\n                    <jats:italic>Borrelia<\/jats:italic>\n                    infections mediated by other ixodid ticks. One of the IpSAP homologs from other ixodid ticks showed similar effects on Lyme spirochete transmission. Together, our findings suggest that LT\u03b2R signaling plays an important role in blocking the transmission and pathogenesis of tick-borne Lyme disease spirochetes, and that IpSAP and its homologs are promising candidates for broad-spectrum vaccine development.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2208274119","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T13:36:06Z","timestamp":1668605766000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":10,"title":["Interference with LT\u03b2R signaling by tick saliva facilitates transmission of Lyme disease spirochetes"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6273-9140","authenticated-orcid":false,"given":"Lin","family":"Jin","sequence":"first","affiliation":[{"name":"Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences\/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China"},{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, Shanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9342-5099","authenticated-orcid":false,"given":"Bao-Gui","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhu","family":"Yin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences\/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, 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