Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Mar 18;17(3):e1009358.
doi: 10.1371/journal.ppat.1009358. eCollection 2021 Mar.

Role of inflammasomes/pyroptosis and PANoptosis during fungal infection

Benoit Briard  1 , R K Subbarao Malireddi  1 , Thirumala-Devi Kanneganti  1
Affiliations
Review

Role of inflammasomes/pyroptosis and PANoptosis during fungal infection

Benoit Briard et al. PLoS Pathog. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Mechanisms of C. albicans-induced inflammasome activation.
(A) C. albicans is recognized by TLRs and Dect receptors to mediate efficient priming and inflammasome activation. The CLR pathway is activated via the adaptor protein SYK, and the downstream supramolecular complex CARD9–Bcl-10–MALT1 drives the recruitment of caspase-8/ASC and/or NLRP3/ASC/caspase-1 to cleave gasdermin D and process and release IL-1β. (B) PAMPs and toxins from C. albicans that can activate the inflammasome have been identified. The C. albicans Saps mediate inflammasome activation. During germination of C. albicans, ECE1 regulates candidalysin toxin production and secretion; candidalysin forms pores in the host cell membrane and induces potassium efflux to cause canonical NLRP3 inflammasome activation. The cell wall, composed of an inner layer (Chitin/β-1,3-glucan/β-1,6-glucan) and an outer layer (mannan), participates in inflammasome activation. ASC, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain; Bcl-10, B-cell lymphoma/leukemia 10; CARD9, caspase activation and recruitment domain-containing protein 9; CLR, C-type lectin receptor; Dect, Dectin; IL-1β, interleukin 1 beta; IL-18, interleukin 18; MALT1, mucosa-associated lymphoid tissue lymphoma translocation protein 1; NLRP3, nucleotide-binding domain and leucine-rich repeat family pyrin domain-containing 3; PAMP, pathogen-associated molecular pattern; Saps, secreted aspartic proteases; SYK, spleen tyrosine kinase; TLR, Toll-like receptor.
Fig 2
Fig 2. Graphical representation of PANoptosome/PANoptosis.
ZBP1 senses C. albicans and A. fumigatus infection to mediate PANoptosome (ZBP1-RIPK1-RIPK3-FADD-CASP8) complex formation and drive PANoptosis, inflammatory cell death characterized by NLRP3/CASP1 activation (pyroptosis), CASP3/CASP7 activation (apoptosis), and MLKL activation (necroptosis). ASC, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain; CARD, caspase activation and recruitment domain; CASP, caspase; DD, death domain; DED, death effector domain; FADD, fas-associated death domain protein; GSDMD, gasdermin D; LRR, leucine-rich repeat; MLKL, mixed lineage kinase domain-like pseudokinase; NLRP3, nucleotide-binding domain and leucine-rich repeat family pyrin domain-containing 3; PYD, pyrin domain; RHIM, receptor-interacting protein homotypic interaction motif; RIPK, receptor-interacting serine/threonine kinase; ZBP1, Z-DNA-binding protein 1.
Fig 3
Fig 3. Mechanisms of A. fumigatus-induced inflammasome activation.
A. fumigatus hyphae induce canonical inflammasome activation after recognition by the CLR and TLR pathways, which is dependent on ROS production and potassium efflux. SYK activation initiates the formation of a supramolecular CARD9–Bcl-10–MALT1 complex to drive MAPKs and NF-κB signaling and induce inflammasome priming. Parallelly, SYK regulates ROS production to mediate the canonical activation of the NLRP3 inflammasome. The NF-κB pathway regulates the expression of IRF1, and the TLR pathway mediates efficient activation of IRF1 after recognition of A. fumigatus via the adaptor molecules MyD88 and TRIF. IRF1 expression and activation induce IRGB10 and ZBP1 expression. IRGB10 targets the fungal cell surface and causes hyphae damage, inhibiting A. fumigatus growth and releasing GAG, β-1,3-glucan, and dsDNA to activate the inflammasome. GAG interacts with ribosomes to block translation, inducing ER stress and NLRP3 inflammasome activation, whereas A. fumigatus dsDNA is recognized by the AIM2 inflammasome. ASC, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain; Bcl-10, B-cell lymphoma/leukemia 10; CARD9, caspase activation and recruitment domain-containing protein 9; CLR, C-type lectin receptor; Dect, dectin; ER, endoplasmic reticulum; GAG, galactosaminogalactan; IL-1β, interleukin 1 beta; IL-18, interleukin 18; IRGB10, immunity-related GTPase B10; IRF1, interferon regulatory factor 1; ITAM, immunoreceptor tyrosine-based activation motif; MALT1, mucosa-associated lymphoid tissue lymphoma translocation protein 1; MAPKs, mitogen activated protein kinases; NF-κB, nuclear factor kappa B; NLRP3, nucleotide-binding domain and leucine-rich repeat family pyrin domain-containing 3; MyD88, myeloid differentiation primary response 88; PAMPs, pathogen-associated molecular patterns; ROS, reactive oxygen species; SYK, spleen tyrosine kinase; TLR, Toll-like receptor; TRIF, Toll/interleukin 1 receptor domain-containing adapter-inducing interferon-β; ZBP1, Z-DNA-binding protein 1.
See this image and copyright information in PMC

References

    1. Man SM, Kanneganti T-D. Converging roles of caspases in inflammasome activation, cell death and innate immunity. Nat Rev Immunol. 2016;16:7–21. 10.1038/nri.2015.7 - DOI - PMC - PubMed
    1. van de Veerdonk FL, Joosten LAB, Netea MG. The interplay between inflammasome activation and antifungal host defense. Immunol Rev. 2015;265: 172–180. 10.1111/imr.12280 - DOI - PubMed
    1. Netea MG, van de Veerdonk FL, van der Meer JWM, Dinarello CA, Joosten LAB. Inflammasome-independent regulation of IL-1-family cytokines. Annu Rev Immunol. 2015;33: 49–77. 10.1146/annurev-immunol-032414-112306 - DOI - PubMed
    1. Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, et al.. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 2015;526:660–5. 10.1038/nature15514 - DOI - PubMed
    1. Kayagaki N, Stowe IB, Lee BL, O’Rourke K, Anderson K, Warming S, et al.. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature. 2015;526:666–71. 10.1038/nature15541 - DOI - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources