Apoptotic caspase inhibits innate immune signaling by cleaving NF-κBs in both Mammals and Flies
Abstract Host organisms use different innate immune mechanisms to defend against pathogenic infections, while tight control of innate immunity is essential for proper immune induction and balance. Here, we reported that apoptotic induction or caspase-3 overexpression caused dramatic reduction of dif...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-08-01
|
| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05156-2 |
| _version_ | 1818082467449405440 |
|---|---|
| author | Di Wu Zhaowei Wang Jing Zhang Adam G. Robinson Bao Lyu Ziyu Chen Chong Wang Bin Wei Xiaojun Xia Qing Zhang Xi Zhou |
| author_facet | Di Wu Zhaowei Wang Jing Zhang Adam G. Robinson Bao Lyu Ziyu Chen Chong Wang Bin Wei Xiaojun Xia Qing Zhang Xi Zhou |
| author_sort | Di Wu |
| collection | DOAJ |
| description | Abstract Host organisms use different innate immune mechanisms to defend against pathogenic infections, while tight control of innate immunity is essential for proper immune induction and balance. Here, we reported that apoptotic induction or caspase-3 overexpression caused dramatic reduction of differently triggered cytokine signalings in human cells, murine primary cells and mouse model, while the loss of caspase-3 or inhibiting apoptosis markedly enhances these immune signalings. Furthermore, caspase-3 can mediate the cleavage of NF-κB members p65/RelA, RelB, and c-Rel via its protease activity. And the caspase-3-resistant p65/RelA, RelB, or c-Rel mutant mostly restored the caspase-3-induced suppression of cytokine production. Interestingly, we further uncovered that apoptotic induction also dramatically inhibited Toll immune signaling in Drosophila, and the Drosophila effector caspases, drICE and DCP-1, also mediated the degradation of DIF, the NF-κB of Toll signaling. Together, our findings demonstrate apoptotic effector caspases, including mammalian caspase-3 and fly drICE/DCP-1, can function as repressors of NF-κB-mediated innate immune signalings. |
| first_indexed | 2024-12-10T19:22:34Z |
| format | Article |
| id | doaj.art-c8bc7c90448a407493260ba8033bcc7e |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-10T19:22:34Z |
| publishDate | 2022-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-c8bc7c90448a407493260ba8033bcc7e2022-12-22T01:36:27ZengNature Publishing GroupCell Death and Disease2041-48892022-08-0113811110.1038/s41419-022-05156-2Apoptotic caspase inhibits innate immune signaling by cleaving NF-κBs in both Mammals and FliesDi Wu0Zhaowei Wang1Jing Zhang2Adam G. Robinson3Bao Lyu4Ziyu Chen5Chong Wang6Bin Wei7Xiaojun Xia8Qing Zhang9Xi Zhou10State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of SciencesState Key Laboratory of Biocontrol, School of Ecology, Sun Yat-sen UniversityLineberger Comprehensive Cancer Center, University of North Carolina School of MedicineLineberger Comprehensive Cancer Center, University of North Carolina School of MedicineState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of SciencesState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of SciencesState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of SciencesState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of SciencesState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterLineberger Comprehensive Cancer Center, University of North Carolina School of MedicineState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of SciencesAbstract Host organisms use different innate immune mechanisms to defend against pathogenic infections, while tight control of innate immunity is essential for proper immune induction and balance. Here, we reported that apoptotic induction or caspase-3 overexpression caused dramatic reduction of differently triggered cytokine signalings in human cells, murine primary cells and mouse model, while the loss of caspase-3 or inhibiting apoptosis markedly enhances these immune signalings. Furthermore, caspase-3 can mediate the cleavage of NF-κB members p65/RelA, RelB, and c-Rel via its protease activity. And the caspase-3-resistant p65/RelA, RelB, or c-Rel mutant mostly restored the caspase-3-induced suppression of cytokine production. Interestingly, we further uncovered that apoptotic induction also dramatically inhibited Toll immune signaling in Drosophila, and the Drosophila effector caspases, drICE and DCP-1, also mediated the degradation of DIF, the NF-κB of Toll signaling. Together, our findings demonstrate apoptotic effector caspases, including mammalian caspase-3 and fly drICE/DCP-1, can function as repressors of NF-κB-mediated innate immune signalings.https://doi.org/10.1038/s41419-022-05156-2 |
| spellingShingle | Di Wu Zhaowei Wang Jing Zhang Adam G. Robinson Bao Lyu Ziyu Chen Chong Wang Bin Wei Xiaojun Xia Qing Zhang Xi Zhou Apoptotic caspase inhibits innate immune signaling by cleaving NF-κBs in both Mammals and Flies Cell Death and Disease |
| title | Apoptotic caspase inhibits innate immune signaling by cleaving NF-κBs in both Mammals and Flies |
| title_full | Apoptotic caspase inhibits innate immune signaling by cleaving NF-κBs in both Mammals and Flies |
| title_fullStr | Apoptotic caspase inhibits innate immune signaling by cleaving NF-κBs in both Mammals and Flies |
| title_full_unstemmed | Apoptotic caspase inhibits innate immune signaling by cleaving NF-κBs in both Mammals and Flies |
| title_short | Apoptotic caspase inhibits innate immune signaling by cleaving NF-κBs in both Mammals and Flies |
| title_sort | apoptotic caspase inhibits innate immune signaling by cleaving nf κbs in both mammals and flies |
| url | https://doi.org/10.1038/s41419-022-05156-2 |
| work_keys_str_mv | AT diwu apoptoticcaspaseinhibitsinnateimmunesignalingbycleavingnfkbsinbothmammalsandflies AT zhaoweiwang apoptoticcaspaseinhibitsinnateimmunesignalingbycleavingnfkbsinbothmammalsandflies AT jingzhang apoptoticcaspaseinhibitsinnateimmunesignalingbycleavingnfkbsinbothmammalsandflies AT adamgrobinson apoptoticcaspaseinhibitsinnateimmunesignalingbycleavingnfkbsinbothmammalsandflies AT baolyu apoptoticcaspaseinhibitsinnateimmunesignalingbycleavingnfkbsinbothmammalsandflies AT ziyuchen apoptoticcaspaseinhibitsinnateimmunesignalingbycleavingnfkbsinbothmammalsandflies AT chongwang apoptoticcaspaseinhibitsinnateimmunesignalingbycleavingnfkbsinbothmammalsandflies AT binwei apoptoticcaspaseinhibitsinnateimmunesignalingbycleavingnfkbsinbothmammalsandflies AT xiaojunxia apoptoticcaspaseinhibitsinnateimmunesignalingbycleavingnfkbsinbothmammalsandflies AT qingzhang apoptoticcaspaseinhibitsinnateimmunesignalingbycleavingnfkbsinbothmammalsandflies AT xizhou apoptoticcaspaseinhibitsinnateimmunesignalingbycleavingnfkbsinbothmammalsandflies |