{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:09:45Z","timestamp":1789153785192,"version":"build-2803163510"},"posted":{"date-parts":[[2026,5,2]]},"group-title":"Immunology","reference-count":43,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["contrat de th\u00e8se (SP)"],"award-info":[{"award-number":["contrat de th\u00e8se (SP)"]}],"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"crossref","award":["Fin de th\u00e8se (SP) FDT202404018322"],"award-info":[{"award-number":["Fin de th\u00e8se (SP) FDT202404018322"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100015326","name":"NIH Common Fund","doi-asserted-by":"crossref","award":["P01 AI168148-01A1 (PI David Haake) to CW"],"award-info":[{"award-number":["P01 AI168148-01A1 (PI David Haake) to CW"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"crossref"}]},{"name":"International consortium research animal disease","award":["S-CR23012-ANR 22 ICRD 0004 01 to CW"],"award-info":[{"award-number":["S-CR23012-ANR 22 ICRD 0004 01 to CW"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Leptospirosis is a neglected zoonotic disease causing \u223c1 million cases and 60,000 deaths annually. Antibiotic therapy can trigger a detrimental inflammatory Jarisch-Herxheimer reaction (JHR). We investigated antibiotic effects in leptospirosis, using a mouse model of severe disease and human whole blood from healthy donors infected ex vivo with bioluminescent\n                  <jats:italic>Leptospira interrogans<\/jats:italic>\n                  . We tested the effect of amoxicillin and ceftriaxone, two bactericidal \u03b2-Lactams antibiotics and assessed bacterial survival, cytokines, pathophysiology and JHR mechanisms upon amoxicillin. \u03b2-lactams induced profound pro-inflammatory cytokine release. In mice, the inflammation was TLR2 and TLR4 dependent, accordingly to the TLR4 host-specificity of LPS recognition, and amoxicillin exacerbated disease severity within hours, notably worsening myocarditis. In human whole blood, this inflammation depended largely on TLR2 (lipoprotein receptor) and TLR5 (flagellin receptor). Interestingly, only stealthy virulent isolates of\n                  <jats:italic>Leptospira interrogans,<\/jats:italic>\n                  unlike some\n                  <jats:italic>Leptospira<\/jats:italic>\n                  species belonging to intermediate and non-virulent clades such as\n                  <jats:italic>biffexa<\/jats:italic>\n                  , induced in human whole blood a JHR-like effect, which was also observed with\n                  <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                  . These findings demonstrate that host-specific TLR recognition of released spirochaetal components by antibiotic treatment drives JHR, evoking a cytokine storm and worsening outcomes.\n                <\/jats:p>","DOI":"10.64898\/2026.04.29.721589","type":"posted-content","created":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T03:50:14Z","timestamp":1777780214000},"source":"Crossref","is-referenced-by-count":0,"title":["\u03b2-Lactam antibiotics trigger mouse TLR2\/4- and human TLR2\/5-dependent Jarisch-Herxheimer reaction in leptospirosis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2611-9832","authenticated-orcid":false,"given":"Stylianos","family":"Papadopoulos","sequence":"first","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM U1306, Unit\u00e9 de Biologie et G\u00e9n\u00e9tique de la Paroi Bact\u00e9rienne, Paris, F-75015, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9945-4285","authenticated-orcid":false,"given":"Thomas","family":"Bernard","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM U1306, Unit\u00e9 de Biologie et G\u00e9n\u00e9tique de la Paroi Bact\u00e9rienne, Paris, F-75015, France"},{"name":"\u00c9cole Normale Sup\u00e9rieure de Lyon, Department of Biology, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorian","family":"Joffres","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM U1306, Unit\u00e9 de Biologie et G\u00e9n\u00e9tique de la Paroi Bact\u00e9rienne, Paris, F-75015, France"},{"name":"\u00c9cole Normale Sup\u00e9rieure Paris-Saclay, Department of Biology, Universit\u00e9 Paris-Saclay, Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3188-9039","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9rique","family":"Vernel-Pauillac","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM U1306, Unit\u00e9 de Biologie et G\u00e9n\u00e9tique de la Paroi Bact\u00e9rienne, Paris, F-75015, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8476-2680","authenticated-orcid":false,"given":"Julie","family":"Cagliero","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM U1306, Unit\u00e9 de Biologie et G\u00e9n\u00e9tique de la Paroi Bact\u00e9rienne, Paris, F-75015, France"},{"name":"Institut Pasteur of New Caledonia, Institut Pasteur International Network, Leptospirosis Research and Expertise Unit, Noum\u00e9a, New Caledonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"COSIPOP study group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3079-5476","authenticated-orcid":false,"given":"Catherine","family":"Werts","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM U1306, Unit\u00e9 de Biologie et G\u00e9n\u00e9tique de la Paroi Bact\u00e9rienne, Paris, F-75015, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091111452534000_2026.04.29.721589v2.1","doi-asserted-by":"crossref","first-page":"e0003898","DOI":"10.1371\/journal.pntd.0003898","article-title":"Global Morbidity and Mortality of Leptospirosis: A Systematic Review","volume":"9","year":"2015","journal-title":"PLOS Neglected Tropical Diseases"},{"key":"2026091111452534000_2026.04.29.721589v2.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trstmh.2010.07.002"},{"key":"2026091111452534000_2026.04.29.721589v2.3","doi-asserted-by":"crossref","unstructured":"Haake, D.A. & Levett, P.N . 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