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Active caspase-1 is able to cleave pro-Interleukin (IL)-1\u03b2, resulting in bioactive IL-1\u03b2. IL-1\u03b2 is a potent proinflammatory cytokine, and thought to play a key role in the pathogenesis of Lyme arthritis, a common manifestation of <jats:italic>Borrelia burgdorferi<\/jats:italic> infection. The precise pathways through which <jats:italic>B. burgdorferi<\/jats:italic> recognition leads to inflammasome activation and processing of IL-1\u03b2 in Lyme arthritis has not been elucidated. In the present study, we investigated the contribution of several pattern recognition receptors and inflammasome components in a novel murine model of Lyme arthritis.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>Lyme arthritis was elicited by live <jats:italic>B. burgdorferi<\/jats:italic>, injected intra-articularly in knee joints of mice. To identify the relevant pathway components, the model was applied to wild-type, NLRP3-\/-, ASC-\/-, caspase-1-\/-, NOD1-\/-, NOD2-\/-, and RICK-\/- mice. As a control, TLR2-\/-, Myd88-\/- and IL-1R-\/- mice were used. Peritoneal macrophages and bone marrow-derived macrophages were used for <jats:italic>in vitro<\/jats:italic> cytokine production and inflammasome activation studies. Joint inflammation was analyzed in synovial specimens and whole knee joints. Mann-Whitney <jats:italic>U<\/jats:italic> tests were used to detect statistical differences.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>We demonstrate that ASC\/caspase-1-driven IL-1\u03b2 is crucial for induction of <jats:italic>B. burgdorferi-<\/jats:italic>induced murine Lyme arthritis. In addition, we show that <jats:italic>B. burgdorferi-<\/jats:italic>induced murine Lyme arthritis is less dependent on NOD1\/NOD2\/RICK pathways while the TLR2-MyD88 pathway is crucial.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>Murine Lyme arthritis is strongly dependent on IL-1 production, and <jats:italic>B. burgdorferi<\/jats:italic> induces inflammasome-mediated caspase-1 activation. Next to that, murine Lyme arthritis is ASC- and caspase-1-dependent, but NLRP3, NOD1, NOD2, and RICK independent. Also, caspase-1 activation by <jats:italic>B. burgdorferi<\/jats:italic> is dependent on TLR2 and MyD88. Based on present results indicating that IL-1 is one of the major mediators in Lyme arthritis, there is a rationale to propose that neutralizing IL-1 activity may also have beneficial effects in chronic Lyme arthritis.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/ar4090","type":"journal-article","created":{"date-parts":[[2012,11,13]],"date-time":"2012-11-13T17:14:27Z","timestamp":1352826867000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Murine Borrelia arthritis is highly dependent on ASC and caspase-1, but independent of NLRP3"],"prefix":"10.1186","volume":"14","author":[{"given":"Marije","family":"Oosting","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrin","family":"Buffen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subbarao RK","family":"Malireddi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Sturm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ineke","family":"Verschueren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marije I","family":"Koenders","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank L","family":"van de Veerdonk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos WM","family":"van der Meer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihai G","family":"Netea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thirumala-Devi","family":"Kanneganti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leo AB","family":"Joosten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,11,13]]},"reference":[{"key":"3820_CR1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1684\/ecn.2009.0179","volume":"21","author":"A Berende","year":"2010","unstructured":"Berende A, Oosting M, Kullberg BJ, Netea MG, Joosten LA: Activation of innate host defense mechanisms by Borrelia. 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