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The \u03b2 form of IL-1 (IL-1\u03b2) is a proinflammatory cytokine released by many cell types and is an important mediator of inflammation during infection. IL-1\u03b2 production is a tightly controlled process that includes regulation at multiple levels and typically requires two distinct signals for activation and release. In this study, we investigated the ability of C. pneumoniae to induce IL-1\u03b2 secretion. We found that C. pneumoniae was unique among the other Chlamydia species tested in its ability to potently induce secretion of mature IL-1\u03b2 from unprimed bone marrow-derived macrophages during a productive infection. TLR2 was required for induction of pro\u2013IL-1\u03b2, whereas the NLRP3\/ASC was required for caspase-1 activation and pro\u2013IL-1\u03b2 cleavage to produce mature IL-1\u03b2. Caspase-1 cleavage was independent of endogenous ATP release, but required potassium flux, lysosomal acidification, and cathepsin B release. We further investigated the role of IL-1 in host defense against C. pneumoniae-induced pneumonia using mice deficient in the type I IL-1R. Although the IL-1R\u2212\/\u2212 mice developed an inflammatory infiltrate, the number of infiltrating neutrophils was lower, whereas there was evidence of increased infiltrating fibroblasts and mesenchymal cells and more lung fibrosis. We conclude that C. pneumoniae directly activates the NLRP3\/ASC inflammasome, leading to the release of biologically active IL-1\u03b2, and that concurrent IL-1 signaling is required for optimal host defense against acute bacterial pneumonia.<\/jats:p>","DOI":"10.4049\/jimmunol.0903937","type":"journal-article","created":{"date-parts":[[2010,4,14]],"date-time":"2010-04-14T22:21:05Z","timestamp":1271283665000},"page":"5743-5754","source":"Crossref","is-referenced-by-count":132,"title":["Inflammation and Fibrosis during\n                    <i>Chlamydia pneumoniae<\/i>\n                    Infection Is Regulated by IL-1 and the NLRP3\/ASC Inflammasome"],"prefix":"10.1093","volume":"184","author":[{"given":"Xianbao","family":"He","sequence":"first","affiliation":[{"name":"Section of Infectious Diseases, Department of Medicine, Boston Medical Center, Boston University School of Medicine , Boston, MA 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samrawit","family":"Mekasha","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Department of Medicine, Boston Medical Center, Boston University School of Medicine , Boston, MA 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Mavrogiorgos","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Department of Medicine, Boston Medical Center, Boston University School of Medicine , Boston, MA 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egil","family":"Lien","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin R","family":"Ingalls","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Department of Medicine, Boston Medical Center, Boston University School of Medicine , Boston, MA 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,5,15]]},"reference":[{"key":"2026012806263756300_r1","doi-asserted-by":"crossref","first-page":"S402","DOI":"10.1086\/315596","article-title":"Background and current knowledge of Chlamydia pneumoniae and atherosclerosis.","volume":"181","author":"Grayston","year":"2000","journal-title":"J. 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