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ZBP1 promotes fungi-induced inflammasome activation and pyroptosis, apoptosis, and necroptosis (PANoptosis)

Cited 103 time in Web of Science Cited 114 time in Scopus
Authors

Banoth, Balaji; Tuladhar, Shraddha; Karki, Rajendra; Sharma, Bhesh Raj; Briard, Benoit; Kesavardhana, Sannula; Burton, Amanda; Kanneganti, Thirumala-Devi

Issue Date
2020-12
Publisher
American Society for Biochemistry and Molecular Biology Inc.
Citation
Journal of Biological Chemistry, Vol.295 No.52, pp.18276-18283
Abstract
Candida albicans and Aspergillus fumigatus are dangerous fungal pathogens with high morbidity and mortality, particularly in immunocompromised patients. Innate immune-mediated programmed cell death (pyroptosis, apoptosis, necroptosis) is an integral part of host defense against pathogens. Inflammasomes, which are canonically formed upstream of pyroptosis, have been characterized as key mediators of fungal sensing and drivers of proinflammatory responses. However, the specific cell death pathways and key upstream sensors activated in the context of Candida and Aspergillus infections are unknown. Here, we report that C. albicans and A. fumigatus infection induced inflammatory programmed cell death in the form of pyroptosis, apoptosis, and necroptosis (PANoptosis). Further, we identified the innate immune sensor Z-DNA binding protein 1 (ZBP1) as the apical sensor of fungal infection responsible for activating the inflammasome/pyroptosis, apoptosis, and necroptosis. The Z alpha 2 domain of ZBP1 was required to promote this inflammasome activation and PANoptosis. Overall, our results demonstrate that C. albicans and A. fumigatus induce PANoptosis and that ZBP1 plays a vital role in inflammasome activation and PANoptosis in response to fungal pathogens.
ISSN
0021-9258
URI
https://hdl.handle.net/10371/203008
DOI
https://doi.org/10.1074/jbc.RA120.015924
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  • College of Natural Sciences
  • School of Biological Sciences
Research Area Cytokine Storm, Host Defense, Innate Immunity in Metabolic and Inflammatory Diseases

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