Commentary Open Access
Volume 2 | Issue 6 | DOI: https://doi.org/https://doi.org/10.33696/immunology.2.064

Newly Identified Function of Caspase-6 in ZBP1-mediated Innate Immune Responses, NLRP3 Inflammasome Activation, PANoptosis, and Host Defense

  • 1Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN, 38105, USA
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Corresponding Author

Thirumala-Devi Kanneganti, Thirumala-Devi.Kanneganti@StJude.org

Received Date: August 21, 2020

Accepted Date: October 12, 2020


Caspase-6 was discovered decades ago, but its roles in biological processes remain largely unknown. Recently, we have demonstrated that caspase-6 plays a critical role in influenza A virus (IAV)-induced cell death and innate immune responses. During IAV infection, Z-DNA binding protein 1 (ZBP1) initiates ZBP1-PANoptosome assembly to drive inflammasome activation and cell death, and we showed that caspase-6 interacts with RIPK3 to enhance the interaction between RIPK3 and ZBP1, thus promoting PANoptosome assembly. Moreover, the caspase activity of caspase-6 is not required for this process, suggesting a caspase-independent function of caspase-6 during IAV infection. Additionally, we found that caspase-6 is required for the alternative activation of alveolar macrophages in response to IAV infection. Our findings provide an opportunity to reconsider the physiological role of caspase-6.


Caspase-6, ZBP1, Influenza A virus, Innate immunity, NLRP3, Inflammasome, RIPK3, RIPK1, Caspase-1, Caspase-8, Pyroptosis, Apoptosis, Necroptosis, PANoptosis, PANoptosome

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