{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:13:13Z","timestamp":1785413593331,"version":"3.56.0"},"reference-count":80,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100009103","name":"Von-Behring-R\u00f6ntgen-Stiftung","doi-asserted-by":"publisher","award":["64-0011"],"award-info":[{"award-number":["64-0011"]}],"id":[{"id":"10.13039\/100009103","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"publisher","award":["TI07.003_Hefter"],"award-info":[{"award-number":["TI07.003_Hefter"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2026,3,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Orientia tsutsugamushi<\/jats:italic>\n                      , the agent of scrub typhus, is an obligate intracellular bacterium whose atypical cell wall lacks many classical pathogen-associated molecular patterns but is enriched in neutral glycans. Its recognition by phagocytes is driven by a heat-stable ligand that triggers innate cytokine responses, yet the nature of this ligand and the receptors sensing it remain incompletely understood. While activation of innate immunity via toll-like (TLR) and nucleotide-binding and oligomerization domain-like receptors has been described, recognition via C-type lectin receptors (CLRs) has remained largely unexplored. Using a flow cytometry-based screening assay with a library of CLR-Fc fusion proteins, we demonstrate binding of\n                      <jats:italic toggle=\"yes\">Orientia<\/jats:italic>\n                      to four mouse CLRs, including Mincle, Dectin-1, Langerin, and DCL-1, as well as to human DC-SIGN. Binding to Mincle was Ca\u00b2\n                      <jats:sup>+<\/jats:sup>\n                      -dependent, indicating carbohydrate-specific recognition. In bone marrow-derived dendritic cells (BMDC), heat-inactivated\n                      <jats:italic toggle=\"yes\">Orientia<\/jats:italic>\n                      induced transcriptional upregulation of Mincle in a MyD88-dependent manner, suggesting cross talk between TLR and CLR pathways. Mincle was dispensable for TNF-\u03b1 induction in BMDC stimulated with\n                      <jats:italic toggle=\"yes\">Orientia<\/jats:italic>\n                      but contributed to the induction of\n                      <jats:italic toggle=\"yes\">interleukin-27<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">cxcl-10<\/jats:italic>\n                      mRNA, indicating an immunomodulatory rather than a classical pro-inflammatory role. We also discuss\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      data that demonstrated upregulation of Mincle and concomitant downregulation of Dectin-1 during\n                      <jats:italic toggle=\"yes\">Orientia<\/jats:italic>\n                      infection. Together, this study identifies multiple CLRs as receptors for\n                      <jats:italic toggle=\"yes\">Orientia<\/jats:italic>\n                      , highlights Mincle as a modulator of innate immunity, and suggests that Mincle-driven immunoregulation helps to shape the inflammatory environment during scrub typhus.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00497-25","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T13:00:51Z","timestamp":1770642051000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["<i>Orientia tsutsugamushi<\/i>\n                    binds to multiple C-type lectin receptors"],"prefix":"10.1128","volume":"94","author":[{"given":"V\u00e9ronique","family":"Hefter","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01rdrb571","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Virology, Philipps University Marburg","place":["Marburg, Germany"]},{"id":[{"id":"https:\/\/ror.org\/01rdrb571","id-type":"ROR","asserted-by":"publisher"}],"name":"German Centre for Infection Research at the Institute of Virology, Philipps University","place":["Marburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Mayer-Lambertz","sequence":"additional","affiliation":[{"name":"Institute for Immunology and Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover","place":["Hanover, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zacharias","family":"Orfanos","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01rdrb571","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Virology, Philipps University Marburg","place":["Marburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Mehl","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01rdrb571","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Virology, Philipps University Marburg","place":["Marburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Lepenies","sequence":"additional","affiliation":[{"name":"Institute for Immunology and Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover","place":["Hanover, Germany"]},{"id":[{"id":"https:\/\/ror.org\/005506478","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Biochemistry and Chemistry, Veterinary Faculty, Ludwig-Maximilians University M\u00fcnchen","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0075-7199","authenticated-orcid":true,"given":"Christian","family":"Keller","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01rdrb571","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Virology, Philipps University Marburg","place":["Marburg, Germany"]},{"id":[{"id":"https:\/\/ror.org\/01rdrb571","id-type":"ROR","asserted-by":"publisher"}],"name":"German Centre for Infection Research at the Institute of Virology, Philipps University","place":["Marburg, Germany"]},{"id":[{"id":"https:\/\/ror.org\/01226dv09","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Medical Microbiology and Hygiene, University Hospital Regensburg","place":["Regensburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2022.12.022"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-019-3903-9"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2009.06.002"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.2.594-602.2000"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1155\/2008\/623145"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611553104"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00185-16"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/dnares\/dsq018"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.55.9.2290-2292.1987"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2010.05.001"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-016-1523-7"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2024.102521"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.03.005"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2022.10.019"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091750"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.06.015"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.12.015"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxab074"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0904013"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1809100115"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.110700"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa218"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805177106"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.09.012"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00861"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1425"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.08.005"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.6.3463"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1408"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1541"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI19655"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.03.012"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021229"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009782"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00213"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2013.12.011"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003096"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1513509112"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63494-3"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02196-17"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.11.7404"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.670219"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003064"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1006\/mpat.2001.0457"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201545858"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301593"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2005.09.002"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.163.9.5039"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.749515"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens12010053"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.03.056"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00075-17"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01196-24"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021787"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838543"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2007.00548.x"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42216-3"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.2c03557"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.3.1686"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/s1074-7613(02)00324-2"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0801162"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1585"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20011983"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.7.3195"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005763"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004991"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003191"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1460"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005765"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005815"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0011445"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxy028"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0173394"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01422"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbx085"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines12121320"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80693-5"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001466"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1778"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.5.2118"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.00497-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.00497-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T14:01:54Z","timestamp":1773151314000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/iai.00497-25"}},"subtitle":[],"editor":[{"given":"Denise M.","family":"Monack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,3,10]]},"references-count":80,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3,10]]}},"alternative-id":["10.1128\/iai.00497-25"],"URL":"https:\/\/doi.org\/10.1128\/iai.00497-25","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,10]]},"assertion":[{"value":"2025-09-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00497-25"}}