title: Acapsular Cryptococcus neoformans activates the NLRP3 inflammasome.
abstract: Cryptococcus neoformans (C. neoformans) is an opportunistic fungal pathogen that mainly infects immunocompromised individuals such as AIDS patients. Although cell surface receptors for recognition of C. neoformans have been studies intensively, cytoplasmic recognition of this pathogen remains unclear. As an important detector of pathogen infection, inflammasome can sense and get activated by infection of various pathogens, including pathogenic fungi such as Candida albicans and Aspergillus fumigatus. Our present study showed that acapsular C. neoformans (cap59Δ) activated the NLRP3-, but not AIM2-nor NLRC4- inflammasome. During this process, viability of the fungus was required. Moreover, our in vivo results showed that during the pulmonary infection of cap59Δ, immune cell infiltration into the lung and effective clearance of the fungus were both dependent on the presence of NLRP3 inflammasome. In summary, our data suggest that the capsule of C. neoformans prevents recognition of the fungus by host NLRP3 inflammasome and indicate that manipulation of inflammasome activity maybe a novel approach to control C. neoformans infection.
authors.affiliation: College of Life and Environmental Sciences, Shanghai Normal University, Shanghai 200235, China; Unit of Innate Immunity, Key Laboratory of Molecular Virology & Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Caiqin
authors.initials: C
authors.lastname: Guo
authors.affiliation: Unit of Innate Immunity, Key Laboratory of Molecular Virology & Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Mingkuan
authors.initials: M
authors.lastname: Chen
authors.affiliation: Unit of Innate Immunity, Key Laboratory of Molecular Virology & Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Shanghai Key Laboratory of Molecular Medical Mycology, Changzheng Hospital, Shanghai 200003, China.
authors.forename: Zhenzong
authors.initials: Z
authors.lastname: Fa
authors.affiliation: Unit of Innate Immunity, Key Laboratory of Molecular Virology & Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Ailing
authors.initials: A
authors.lastname: Lu
authors.affiliation: Shanghai Key Laboratory of Molecular Medical Mycology, Changzheng Hospital, Shanghai 200003, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fang
authors.affiliation: Unit of Innate Immunity, Key Laboratory of Molecular Virology & Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
authors.affiliation: Unit of Innate Immunity, Key Laboratory of Molecular Virology & Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Changbin
authors.initials: C
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory of Molecular Medical Mycology, Changzheng Hospital, Shanghai 200003, China. Electronic address: liaowanqing@sohu.com.
authors.forename: Wanqing
authors.initials: W
authors.lastname: Liao
authors.affiliation: Unit of Innate Immunity, Key Laboratory of Molecular Virology & Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: gxmeng@ips.ac.cn.
authors.forename: Guangxun
authors.initials: G
authors.lastname: Meng
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003453:Cryptococcosis / Q000276:immunology / Q000473:pathology; D003455:Cryptococcus neoformans / Q000472:pathogenicity*; D004195:Disease Models, Animal; D005260:Female; D020868:Gene Silencing; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D058847:Inflammasomes / Q000235:genetics / Q000378:metabolism*; D020382:Interleukin-18 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D050296:Microbial Viability; D009154:Mutation; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017382:Reactive Oxygen Species / Q000378:metabolism; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017382:Reactive Oxygen Species; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha
keywords: Capsule; Cryptococcus neoformans; Glucuronoxylomannan; Inflammasome; NLRP3