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However, intracellular sensing of this pathogen is still poorly understood. Our previous studies have demonstrated that both biofilm and acapsular mutant of C. neoformans are able to activate the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome. In the current study, it was found that opsonization-mediated internalization of encapsulated C. neoformans also activated the canonical NLRP3\u2013apoptosis-associated speck-like protein containing a CARD (ASC)\u2013caspase-1 inflammasome. In addition, the internalized C. neoformans activated the noncanonical NLRP3\u2013ASC\u2013caspase-8 inflammasome as well, which resulted in robust IL-1\u03b2 secretion and cell death from caspase-1\u2013deficient primary dendritic cells. Interestingly, we found that caspase-1 was inhibitory for the activation of caspase-8 in dendritic cells upon C. neorformans challenge. Further mechanistic studies showed that both phagolysosome membrane permeabilization and potassium efflux were responsible for C. neoformans\u2013induced activation of either the canonical NLRP3\u2013ASC\u2013caspase-1 inflammasome or the noncanonical NLRP3\u2013ASC\u2013caspase-8 inflammasome. Moreover, challenge with zymosan also led to the activation of the noncanonical NLRP3\u2013ASC\u2013caspase-8 inflammasome in cells absent for caspase-1. Collectively, these findings uncover a number of novel signaling pathways for the innate immune response of host cells to C. neoformans infection and suggest that manipulating NLRP3 signaling may help to control fungal challenge.<\/jats:p>","DOI":"10.4049\/jimmunol.1500865","type":"journal-article","created":{"date-parts":[[2015,10,15]],"date-time":"2015-10-15T03:28:31Z","timestamp":1444879711000},"page":"4962-4972","source":"Crossref","is-referenced-by-count":68,"title":["Internalized <i>Cryptococcus neoformans<\/i> Activates the Canonical Caspase-1 and the Noncanonical Caspase-8 Inflammasomes"],"prefix":"10.1093","volume":"195","author":[{"given":"Mingkuan","family":"Chen","sequence":"first","affiliation":[{"name":"Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Xing","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ailing","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Fang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Molecular Medical Mycology, Changzheng Hospital , Shanghai 200003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changbin","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanqing","family":"Liao","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Molecular Medical Mycology, Changzheng Hospital , Shanghai 200003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangxun","family":"Meng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,11,15]]},"reference":[{"key":"2025030704242580300_r1","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern recognition receptors and inflammation","volume":"140","author":"Takeuchi","year":"2010","journal-title":"Cell"},{"key":"2025030704242580300_r2","doi-asserted-by":"crossref","first-page":"a016287","DOI":"10.1101\/cshperspect.a016287","article-title":"Inflammasomes","volume":"6","author":"de Zoete","year":"2014","journal-title":"Cold Spring Harb. 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