The NLRP3 inflammasome activation in human or mouse cells, sensitivity causes puzzle

Wang, Hongbin; Mao, Liming; Meng, Guangxun

doi:10.1007/s13238-013-3905-0

Cited by 40 publications

(34 citation statements)

References 24 publications

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“…Thus, canonical caspase-1 inflammasome and noncanonical caspase-8 inflammasome coordinate to mount innate immune responses against fungal pathogens. macrophages (61). As a facultative intracellular fungal pathogen, C. neoformans can replicate in host phagocytic cells (62,63).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…The activation of NLRP3 inflammasome is tightly regulated by two-step signals. 4 The first priming signal, such as lipopolysaccharide (LPS), enhances the expression of inflammasome components and target proteins through activation of transcription factor NF-jB. The second activation signal promotes the assembly of inflammasome components.…”

Section: Introductionmentioning

confidence: 99%

Reactive astrocytes and perivascular macrophages express NLRP3 inflammasome in active demyelinating lesions of multiple sclerosis and necrotic lesions of neuromyelitis optica and cerebral infarction

Kawana

Yamamoto

Ishida³

et al. 2013

Clinical & Exp Neuroim

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Objective Inflammasome, activated by pathogen-derived and host-derived danger signals, constitutes a multimolecular signaling complex that serves as a platform for caspase-1 (CASP1) activation and interleukin-1b (IL-1B) maturation. Mice deficient for NLRP3 inflammasome components are resistant to experimental autoimmune encephalomyelitis (EAE), suggesting a pro-inflammatory role of NLRP3 inflammasome. However, at present, a pathological role of NLRP3 inflammasome in multiple sclerosis (MS) brains remains unknown. Methods We studied the expression of NLRP3 inflammasome components in active demyelinating lesions of MS by immunohistochemistry. Results Reactive astrocytes and perivascular macrophages expressed all three components of NLRP3 inflammasome -NLRP3, ASC and CASP1 -along with IL-1B in active demyelinating lesions of MS, active necrotic lesions of neuromyelitis optica (NMO) and acute necrotic lesions of cerebral infarction. In contrast, the levels of expression of NLRP3, ASC, CASP1, and IL-1B were greatly reduced in chronic inactive lesions of MS and gliotic lesions of cerebral infarction. Furthermore, the great majority of ramified and amoeboid microglia did not express NLRP3 in active and inactive MS lesions. Conclusions NLRP3 inflammasome could be activated chiefly in reactive astrocytes and infiltrating macrophages under the condition of active destruction of brain tissues that potentially provides a danger signal. (

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“…To elucidate the potential link between HBV and the inflammasome/caspase‐1 signaling pathway, we performed a series of experiments on HepG2, HepG2.2.15, and HepAD38 cell lines. IFN‐α triggers inflammasome activation via upregulation and activation of AIM2, while LPS is an effective inducer of NLRP‐3 and NLRC‐4 . After treatment of cells with LPS + ATP or IFN‐α + Poly(dA:dT), protein and supernatant samples were extracted.…”

Section: Resultsmentioning

confidence: 96%

HBV‐Pol is crucial for HBV‐mediated inhibition of inflammasome activation and IL‐1β production

Lei

Kong

et al. 2019

Liver International

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Background & Aims: Hepatitis B virus (HBV) infection is the most critical factor underlying liver cirrhosis and hepatocellular carcinoma worldwide. IL-1β and IL-18, generated by activation of the inflammasome/caspase-1 signaling pathway, play important roles in the control and clearance of HBV. However, the specific relationship between the inflammasome response and IFN-α resistance or viral persistence is yet to be established. Methods: Blood samples of patients and supernatant fractions of HBV cell lines were collected for analysis and the effects on inflammasome activation and IL-1β production evaluated via enzyme-linked immunosorbent assay (ELISA), western blot, quantitative RT-PCR and immunofluorescence. Results: IL-1β and IL-18 levels produced in sera of IFN-α non-responders were significantly lower than those of responders and normal donors. Additionally, expression of IL-1β and inflammasome components was decreased in peripheral blood mononuclear cells (PBMC) of non-responders, compared with those of responders. In vitro experiments on HepG2, HepG2.2.15 and HepAD38 cell lines showed that HBV induces a significant decrease in IL-1β production through inhibiting activation of the NF-κB signaling and inflammasome/caspase-1 pathways. And hepatitis B virus polymerase (HBV-Pol) appeared crucial for these inhibitory effects of HBV.Conclusion: IL-1β production is suppressed in HBV carriers and IFN-α non-responders. HBV induces a significant decrease in IL-1β production through inhibiting the NF-κB signaling and inflammasome pathways, for which HBV-Pol is a crucial requirement.

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The NLRP3 inflammasome activation in human or mouse cells, sensitivity causes puzzle

Cited by 40 publications

References 24 publications

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

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

Reactive astrocytes and perivascular macrophages express NLRP3 inflammasome in active demyelinating lesions of multiple sclerosis and necrotic lesions of neuromyelitis optica and cerebral infarction

HBV‐Pol is crucial for HBV‐mediated inhibition of inflammasome activation and IL‐1β production

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