tetano
Editor, Senior Moderator
J Immunol
. 2021 Oct 18;ji2100757.
doi: 10.4049/jimmunol.2100757. Online ahead of print.
Cutting Edge: Caspase-8 Is a Linchpin in Caspase-3 and Gasdermin D Activation to Control Cell Death, Cytokine Release, and Host Defense during Influenza A Virus Infection
Yaqiu Wang[SUP] 1 [/SUP], Rajendra Karki[SUP] 1 [/SUP], Min Zheng[SUP] 1 [/SUP], Balabhaskararao Kancharana[SUP] 1 [/SUP], SangJoon Lee[SUP] 1 [/SUP], Sannula Kesavardhana[SUP] 1 [/SUP], Baranda S Hansen[SUP] 2 [/SUP], Shondra M Pruett-Miller[SUP] 2 [/SUP], Thirumala-Devi Kanneganti[SUP] 3 [/SUP]
Affiliations
Abstract
Programmed cell death (PCD) is essential for the innate immune response, which serves as the first line of defense against pathogens. Caspases regulate PCD, immune responses, and homeostasis. Caspase-8 specifically plays multifaceted roles in PCD pathways including pyroptosis, apoptosis, and necroptosis. However, because caspase-8-deficient mice are embryonically lethal, little is known about how caspase-8 coordinates different PCD pathways under physiological conditions. Here, we report an anti-inflammatory role of caspase-8 during influenza A virus infection. We generated viable mice carrying an uncleavable version of caspase-8 (Casp8 [SUP]DA/DA[/SUP]). We demonstrated that caspase-8 autoprocessing was responsible for activating caspase-3, thereby suppressing gasdermin D-mediated pyroptosis and inflammatory cytokine release. We also found that apoptotic and pyroptotic pathways were activated at the same time during influenza A virus infection, which enabled the cell-intrinsic anti-inflammatory function of the caspase-8-caspase-3 axis. Our findings provide new insight into the immunological consequences of caspase-8-coordinated PCD cross-talk under physiological conditions.
. 2021 Oct 18;ji2100757.
doi: 10.4049/jimmunol.2100757. Online ahead of print.
Cutting Edge: Caspase-8 Is a Linchpin in Caspase-3 and Gasdermin D Activation to Control Cell Death, Cytokine Release, and Host Defense during Influenza A Virus Infection
Yaqiu Wang[SUP] 1 [/SUP], Rajendra Karki[SUP] 1 [/SUP], Min Zheng[SUP] 1 [/SUP], Balabhaskararao Kancharana[SUP] 1 [/SUP], SangJoon Lee[SUP] 1 [/SUP], Sannula Kesavardhana[SUP] 1 [/SUP], Baranda S Hansen[SUP] 2 [/SUP], Shondra M Pruett-Miller[SUP] 2 [/SUP], Thirumala-Devi Kanneganti[SUP] 3 [/SUP]
Affiliations
- PMID: 34663620
- DOI: 10.4049/jimmunol.2100757
Abstract
Programmed cell death (PCD) is essential for the innate immune response, which serves as the first line of defense against pathogens. Caspases regulate PCD, immune responses, and homeostasis. Caspase-8 specifically plays multifaceted roles in PCD pathways including pyroptosis, apoptosis, and necroptosis. However, because caspase-8-deficient mice are embryonically lethal, little is known about how caspase-8 coordinates different PCD pathways under physiological conditions. Here, we report an anti-inflammatory role of caspase-8 during influenza A virus infection. We generated viable mice carrying an uncleavable version of caspase-8 (Casp8 [SUP]DA/DA[/SUP]). We demonstrated that caspase-8 autoprocessing was responsible for activating caspase-3, thereby suppressing gasdermin D-mediated pyroptosis and inflammatory cytokine release. We also found that apoptotic and pyroptotic pathways were activated at the same time during influenza A virus infection, which enabled the cell-intrinsic anti-inflammatory function of the caspase-8-caspase-3 axis. Our findings provide new insight into the immunological consequences of caspase-8-coordinated PCD cross-talk under physiological conditions.