期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 295, 期 52, 页码 18276-18283出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.RA120.015924
关键词
cell death; inflammasome; PANoptosis; PANoptosome; pyroptosis; apoptosis; necroptosis; ZBP1; gasdermin D; MLKL; RIPK3; caspase-1; caspase-8; caspase-3; caspase-7; Aspergillus fumigatus; Candida albicans; fungi; infection; infectious disease; host defense
资金
- US National Institutes of Health [AI101935, AI124346, AR056296, CA253095]
- American Lebanese Syrian Associated Charities
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.
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