Biofilm from a clinical strain of Cryptococcus neoformans activates the NLRP3 inflammasome

Lei, Guowei; Chen, Mingkuan; Li, Hua; Niu, Jianlou; Wu, Shuangyan; Mao, Liming; Lu, Ailing; Wang, Hongbin; Chen, Wei; Xu, Bin; Leng, Qibin; Xu, Chi; An, Liguo; Zhu, Liping; Meng, Guangxun

doi:10.1038/cr.2013.49

Cited by 44 publications

(56 citation statements)

References 14 publications

(15 reference statements)

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“…All these fungi were recently reported to be sensed by the NLRP3 inflammasome and to trigger the secretion of IL-1␤ from both mouse and human cells (31)(32)(33)(34). These data and our findings in the present study indicated that NLRP3 plays an important role in the host defense against fungal infection.…”

Section: Discussionsupporting

confidence: 80%

“…The role of inflammasomes in host immune responses toward Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans has also been described (31)(32)(33)(34). All these fungi activate the NLRP3 inflammasome (31)(32)(33)(34), and NLRP10 is also important for antifungal immunity against Candida albicans (35). Until now, whether dermatophytes such as M.…”

mentioning

confidence: 99%

“…Recent reports showed that a number of PRRs are involved in the host immune responses against fungal infections (26)(27)(28)(29)(30). The role of inflammasomes in host immune responses toward Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans has also been described (31)(32)(33)(34). All these fungi activate the NLRP3 inflammasome (31)(32)(33)(34), and NLRP10 is also important for antifungal immunity against Candida albicans (35).…”

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confidence: 99%

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Pathogenic Fungus Microsporum canis Activates the NLRP3 Inflammasome

Mao

Zhang

et al. 2014

Infect Immun

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Microsporum canis is a pathogenic fungus with worldwide distribution that causes tinea capitis in animals and humans. M. canis also causes invasive infection in immunocompromised patients. To defy pathogenic fungal infection, the host innate immune system is the first line of defense. As an important arm of innate immunity, the inflammasomes are intracellular multiprotein complexes that control the activation of caspase-1, which cleaves proinflammatory cytokine pro-interleukin-1␤ (IL-1␤) into its mature form. To determine whether the inflammasome is involved in the host defense against M. canis infection, we challenged human monocytic THP-1 cells and mouse dendritic cells with a clinical strain of M. canis isolated from patients with tinea capitis. We found that M. canis infection triggered rapid secretion of IL-1␤ from both THP-1 cells and mouse dendritic cells. Moreover, by using gene-specific shRNA and competitive inhibitors, we determined that M. canis-induced IL-1␤ secretion was dependent on NLRP3. The pathways proposed for NLRP3 inflammasome activation, namely, cathepsin B activity, K ؉ efflux, and reactive oxygen species production, were all required for the inflammasome activation triggered by M. canis. Meanwhile, Syk, Dectin-1, and Card9 were found to be involved in M. canis-induced IL-1␤ secretion via regulation of pro-IL-1␤ transcription. More importantly, our data revealed that M. canis-induced production of IL-1␤ was dependent on the NLRP3 inflammasome in vivo. Together, this study unveils that the NLRP3 inflammasome exerts a critical role in host innate immune responses against M. canis infection, and our data suggest that diseases that result from M. canis infection might be controlled by regulating the activation of inflammasomes.

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Section: Discussionsupporting

confidence: 80%

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confidence: 99%

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confidence: 99%

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Pathogenic Fungus Microsporum canis Activates the NLRP3 Inflammasome

Mao

Zhang

et al. 2014

Infect Immun

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“…When NLRP3 is activated, it recruits several peptides including pro-caspase-1 to form the NLRP3 inflammasome, activating caspase-1 and eventually leading to the cleaving of pro-IL-1b to IL-1b. The capacity of P. brasiliensis to activate the NLRP3 inflammasome are in agreement with previous studies using C. albicans, A. fumigatus and C. neoformans [105][106][107] and suggest that manipulating NLRP3 inflammasome activation may provide a new approach for the control of PCM. 104 Glycoprotein 43 (gp43) was first described in 1986, and it is the major diagnostic antigen of P. brasiliensis.…”

Section: Dendritic Cells In the Immune Responsesupporting

confidence: 77%

Dendritic cell interactions withHistoplasmaandParacoccidioides

2015

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“…In addition, research from the Meng Laboratory also revealed that the biofilm from C. neoformans as well as the acapsular mutant of C. neoformans both activated the NLRP3 inflammasome (12,13). However, whether encapsulated C. neoformans activates inflammasome under certain conditions is not known yet.…”

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confidence: 99%

Internalized Cryptococcus neoformans Activates the Canonical Caspase-1 and the Noncanonical Caspase-8 Inflammasomes

Chen

Xing

et al. 2015

The Journal of Immunology

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Cryptococcus neoformans is an opportunistic fungal pathogen that causes cryptococccosis in immunocompromised patients as well as immunocompetent individuals. Host cell surface receptors that recognize C. neoformans have been widely studied. 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–apoptosis-associated speck-like protein containing a CARD (ASC)–caspase-1 inflammasome. In addition, the internalized C. neoformans activated the noncanonical NLRP3–ASC–caspase-8 inflammasome as well, which resulted in robust IL-1β secretion and cell death from caspase-1–deficient 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–induced activation of either the canonical NLRP3–ASC–caspase-1 inflammasome or the noncanonical NLRP3–ASC–caspase-8 inflammasome. Moreover, challenge with zymosan also led to the activation of the noncanonical NLRP3–ASC–caspase-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.

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Biofilm from a clinical strain of Cryptococcus neoformans activates the NLRP3 inflammasome

Cited by 44 publications

References 14 publications

Pathogenic Fungus Microsporum canis Activates the NLRP3 Inflammasome

Pathogenic Fungus Microsporum canis Activates the NLRP3 Inflammasome

Dendritic cell interactions withHistoplasmaandParacoccidioides

Internalized Cryptococcus neoformans Activates the Canonical Caspase-1 and the Noncanonical Caspase-8 Inflammasomes

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