Co-activation of Caspase-1 and Caspase-8 in CMV-induced SGN death by inflammasome-associated pyroptosis and apoptosis

  • Int Immunopharmacol. 2022 Oct 14;113(Pt A):109305. doi: 10.1016/j.intimp.2022.109305.
Menghua Li  1 ,  Liyuan Wu  2 ,  Mengbing Chen  3 ,  Yanfen Dong  4 ,  Liting Zheng  4 ,  Daishi Chen  1 ,  Yuehua Qiao  5 ,  Zhaoyang Ke  6 ,  Xi Shi  7
Affiliations
  • 1. Department of Otolaryngology, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen 518020, China; The First Affiliated Hospital, Jinan University, Guangzhou 510632, China.
  • 2. Artificial Auditory Laboratory of Jiangsu Province, Xuzhou Medical University, Xuzhou 221000, China; The Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, China.
  • 3. Ankang People's Hospital, Ankang 725000, China.
  • 4. Artificial Auditory Laboratory of Jiangsu Province, Xuzhou Medical University, Xuzhou 221000, China.
  • 5. Artificial Auditory Laboratory of Jiangsu Province, Xuzhou Medical University, Xuzhou 221000, China. Electronic address: [email protected].
  • 6. Department of Otolaryngology, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen 518020, China; The First Affiliated Hospital, Jinan University, Guangzhou 510632, China. Electronic address: [email protected].
  • 7. Artificial Auditory Laboratory of Jiangsu Province, Xuzhou Medical University, Xuzhou 221000, China. Electronic address: [email protected].
PMID: 36244217 DOI: 10.1016/j.intimp.2022.109305
Abstract

Cytomegalovirus (CMV) Infection causes newborn deafness, and the death of the spiral ganglion neurons (SGNs) is crucial in determining the degree of CMV-related hearing loss. Therefore, understanding the psychopathology of CMV-related SGN loss is important for identifying targets and exploring treatment strategies. In this study, we found that Pyroptosis and Apoptosis, two inflammasome-related programmed cell death pathways, are involved in CMV-induced SGN death and are mainly regulated by activated Caspase-1 and Caspase-8. Moreover, suppressing inflammasome assembly by blocking apoptosis-associated speck-like protein containing a CARD (ASC) interaction inhibited the activation of both Caspase-1 and Caspase-8, rescued SGN death, and improved hearing loss in CMV-infected newborn mice. Therefore, we propose that ASC inflammasome might be a promising target for treating CMV-related SGN death and newborn hearing loss by inhibiting Caspase-1 and Caspase-8 activated Pyroptosis and Apoptosis.

Keywords
ASC-inflammasome; Apoptosis; Cytomegalovirus infection; Hearing loss; Pyroptosis.
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