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In this work, we demonstrate that L. interrogans induces NLRP3 inflammasome-dependent secretion of IL-1\u03b2 through the alteration of potassium transport in bone marrow-derived macrophages. Lysosome destabilization also contributed to the IL-1\u03b2 production upon stimulation with live, but not dead, bacteria. Using bone marrow-derived macrophages from various TLRs and nucleotide-binding oligomerization domain-deficient mice, we further determined that IL-1\u03b2 production was dependent on TLR2 and TLR4, suggesting a participation of the leptospiral LPS to this process. Hypokaliemia in leptospirosis has been linked to the presence of glycolipoprotein, a cell wall component of L. interrogans that is known to inhibit the expression and functions of the Na\/K-ATPase pump. We show in this study that glycolipoprotein activates the inflammasome and synergizes with leptospiral LPS to produce IL-1\u03b2, mimicking the effect of whole bacteria. These results were confirmed in vivo, as wild-type mice expressed more IL-1\u03b2 in the kidney than TLR2\/4-deficient mice 3 d postinfection with L. interrogans. Collectively, these findings provide the first characterization, to our knowledge, of bacteria-induced activation of the NLRP3 inflammasome through the downregulation of a specific host potassium transporter.<\/jats:p>","DOI":"10.4049\/jimmunol.1101987","type":"journal-article","created":{"date-parts":[[2012,2,9]],"date-time":"2012-02-09T12:13:30Z","timestamp":1328789610000},"page":"2805-2814","source":"Crossref","is-referenced-by-count":77,"title":["Downregulation of the Na\/K-ATPase Pump by Leptospiral Glycolipoprotein Activates the NLRP3 Inflammasome"],"prefix":"10.1093","volume":"188","author":[{"given":"Sonia","family":"Lacroix-Lamand\u00e9","sequence":"first","affiliation":[{"name":"Institut Pasteur, G5 Biologie et G\u00e9n\u00e9tique de la Paroi Bact\u00e9rienne , Paris 75724 ,","place":["France"]},{"name":"INSERM Groupe Avenir , Paris 75015 ,","place":["France"]},{"name":"Institut National de la Recherche Agronomique, Infectiologie Animale et Sant\u00e9 Publique , Nouzilly 37380 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Fanton d\u2019Andon","sequence":"additional","affiliation":[{"name":"Institut Pasteur, G5 Biologie et G\u00e9n\u00e9tique de la Paroi Bact\u00e9rienne , Paris 75724 ,","place":["France"]},{"name":"INSERM Groupe Avenir , Paris 75015 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Michel","sequence":"additional","affiliation":[{"name":"Institut Pasteur, G5 Biologie et G\u00e9n\u00e9tique de la Paroi Bact\u00e9rienne , Paris 75724 ,","place":["France"]},{"name":"INSERM Groupe Avenir , Paris 75015 ,","place":["France"]},{"name":"Institut de Biologie de l\u2019Ecole Normale Superieure-Unit\u00e9 Mixte de Recherche 7618 Bioemco , Paris 75230 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwenn","family":"Ratet","sequence":"additional","affiliation":[{"name":"Institut Pasteur, G5 Biologie et G\u00e9n\u00e9tique de la Paroi Bact\u00e9rienne , Paris 75724 ,","place":["France"]},{"name":"INSERM Groupe Avenir , Paris 75015 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana J","family":"Philpott","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 1A1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen E","family":"Girardin","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto , Toronto, Ontario M5S 1A1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo G","family":"Boneca","sequence":"additional","affiliation":[{"name":"Institut Pasteur, G5 Biologie et G\u00e9n\u00e9tique de la Paroi Bact\u00e9rienne , Paris 75724 ,","place":["France"]},{"name":"INSERM Groupe Avenir , Paris 75015 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Vandewalle","sequence":"additional","affiliation":[{"name":"INSERM U773 , Paris 75018 ,","place":["France"]},{"name":"Universit\u00e9 Paris Diderot Sorbonne Paris Cit\u00e9 , Paris 75013 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Werts","sequence":"additional","affiliation":[{"name":"Institut Pasteur, G5 Biologie et G\u00e9n\u00e9tique de la Paroi Bact\u00e9rienne , Paris 75724 ,","place":["France"]},{"name":"INSERM Groupe Avenir , Paris 75015 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,3,15]]},"reference":[{"key":"2025032409592611900_r1","first-page":"109","article-title":"Leptospirosis in Taiwan\u2014an underestimated infectious disease","volume":"30","author":"Yang","year":"2007","journal-title":"Chang Gung Med. 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