{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:34:03Z","timestamp":1791304443953,"version":"4.3.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2009,8,1]],"date-time":"2009-08-01T00:00:00Z","timestamp":1249084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Leptospirosis is a widespread zoonosis caused by pathogenic Leptospira interrogans that are transmitted by asymptomatic infected rodents. Leptospiral lipoproteins and LPS have been shown to stimulate murine cells via TLRs 2 and 4. Host defense mechanisms remain obscure, although TLR4 has been shown to be involved in clearing Leptospira. In this study, we show that double (TLR2 and TLR4) knockout (DKO) mice rapidly died from severe hepatic and renal failure following Leptospira inoculation. Strikingly, the severe proinflammatory response detected in the liver and kidney from Leptospira-infected DKO mice appears to be independent of MyD88, the main adaptor of TLRs. Infection of chimeric mice constructed with wild-type and DKO mice, and infection of several lines of transgenic mice devoid of T and\/or B lymphocytes, identified B cells as the crucial lymphocyte subset responsible for the clearance of Leptospira, through the early production of specific TLR4-dependent anti-Leptospira IgMs elicited against the leptospiral LPS. We also found a protective tissue compartmentalized TLR2\/TLR4-mediated production of IFN-\u03b3 by B and T lymphocytes, in the liver and kidney, respectively. In contrast, the tissue inflammation observed in Leptospira-infected DKO mice was further characterized to be mostly due to B lymphocytes in the liver and T cells in the kidney. Altogether these findings demonstrate that TLR2 and TLR4 play a key role in the early control of leptospirosis, but do not directly trigger the inflammation induced by pathogenic Leptospira.<\/jats:p>","DOI":"10.4049\/jimmunol.0900506","type":"journal-article","created":{"date-parts":[[2009,7,27]],"date-time":"2009-07-27T21:30:07Z","timestamp":1248730207000},"page":"2669-2677","source":"Crossref","is-referenced-by-count":134,"title":["TLR4- and TLR2-Mediated B Cell Responses Control the Clearance of the Bacterial Pathogen,\n                    <i>Leptospira interrogans<\/i>"],"prefix":"10.1093","volume":"183","author":[{"given":"C\u00e9cilia","family":"Chassin","sequence":"first","affiliation":[{"name":"INSERM, U773, Centre de Recherche Biom\u00e9dicale Bichat-Beaujon (CRB3) , BP 416, Paris France; Universit\u00e9 Paris 7-Denis Diderot, Site Bichat, Paris, Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Picardeau","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Postulante Biologie des Spiroch\u00e8tes"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Michel","family":"Goujon","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Poitiers, Unit\u00e9 de Pathologie Ultrastructurale et Exp\u00e9rimentale, Universit\u00e9 de Poitiers , Poitiers,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Bourhy","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Postulante Biologie des Spiroch\u00e8tes"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Quellard","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Poitiers, Unit\u00e9 de Pathologie Ultrastructurale et Exp\u00e9rimentale, Universit\u00e9 de Poitiers , Poitiers,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Darche","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de R\u00e9ponses Pr\u00e9coces aux Parasites et Immunopathologie"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Badell","sequence":"additional","affiliation":[{"name":"Unit\u00e9 G\u00e9n\u00e9tique Mycobact\u00e9rienne"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine Fanton","family":"d'Andon","sequence":"additional","affiliation":[{"name":"G5 Biologie et G\u00e9n\u00e9tique de la Paroi Bact\u00e9rienne"},{"name":"INSERM, Groupe Avenir , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Winter","sequence":"additional","affiliation":[{"name":"Unit\u00e9 G\u00e9n\u00e9tique Mycobact\u00e9rienne"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Lacroix-Lamand\u00e9","sequence":"additional","affiliation":[{"name":"Institut National de Recherche Agronomique, U1282, Infectiologie Animale et Sant\u00e9 Publique , Nouzilly, ; Institut Pasteur","place":["France"]},{"name":"G5 Biologie et G\u00e9n\u00e9tique de la Paroi Bact\u00e9rienne"},{"name":"INSERM, Groupe Avenir , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Buzoni-Gatel","sequence":"additional","affiliation":[{"name":"Institut National de Recherche Agronomique, U1282, Infectiologie Animale et Sant\u00e9 Publique , Nouzilly, ; Institut Pasteur","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Vandewalle","sequence":"additional","affiliation":[{"name":"INSERM, U773, Centre de Recherche Biom\u00e9dicale Bichat-Beaujon (CRB3) , BP 416, Paris France; Universit\u00e9 Paris 7-Denis Diderot, Site Bichat, Paris, Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Werts","sequence":"additional","affiliation":[{"name":"G5 Biologie et G\u00e9n\u00e9tique de la Paroi Bact\u00e9rienne"},{"name":"INSERM, Groupe Avenir , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,8,15]]},"reference":[{"key":"2026012811285320700_R1","first-page":"757","article-title":"Leptospirosis: a zoonotic disease of global importance.","volume-title":"Lancet Infect. 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