Stimulation of PSTPIP1 to trigger proinflammatory responses in asymptomatic SARS-CoV-2 infections
Ruili Ji,
Yue Wu,
Yuhua Ye,
Yanling Li,
Yizhe Li,
Guojiu Zhong,
Wentao Fan,
Chengjuan Feng,
Hui Chen,
Xiangyun Teng,
Yunli Wu,
Jianhua Xu
Affiliations
Ruili Ji
Department of Laboratory Medicine, Shunde Hospital of Guangzhou University of Chinese Medicine, Foshan, China
Yue Wu
Department of Laboratory Medicine, Shunde Hospital of Guangzhou University of Chinese Medicine, Foshan, China
Yuhua Ye
Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, China
Yanling Li
Guangzhou Huayin Medical Laboratory Center Ltd., Guangzhou, Guangdong, China
Yizhe Li
Department of Laboratory Medicine, Shunde Hospital of Guangzhou University of Chinese Medicine, Foshan, China; Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, China; Guangzhou Huayin Medical Laboratory Center Ltd., Guangzhou, Guangdong, China; Department of Respiratory, Maoming Hospital of Guangzhou University of Chinese Medicine, Maoming 525000, Guangdong, China; Department of Clinical Laboratory, Maoming Hospital of Guangzhou University of Chinese Medicine, Maoming 525000, Guangdong, China; Department of Laboratory Science, West China TianFu Hospital, Sichuan University, Sichuan, China
Guojiu Zhong
Department of Respiratory, Maoming Hospital of Guangzhou University of Chinese Medicine, Maoming 525000, Guangdong, China
Wentao Fan
Guangzhou Huayin Medical Laboratory Center Ltd., Guangzhou, Guangdong, China
Chengjuan Feng
Department of Clinical Laboratory, Maoming Hospital of Guangzhou University of Chinese Medicine, Maoming 525000, Guangdong, China
Hui Chen
Guangzhou Huayin Medical Laboratory Center Ltd., Guangzhou, Guangdong, China
Xiangyun Teng
Department of Clinical Laboratory, Maoming Hospital of Guangzhou University of Chinese Medicine, Maoming 525000, Guangdong, China; Corresponding author.
Yunli Wu
Guangzhou Huayin Medical Laboratory Center Ltd., Guangzhou, Guangdong, China; Corresponding author.
Jianhua Xu
Department of Laboratory Medicine, Shunde Hospital of Guangzhou University of Chinese Medicine, Foshan, China; Department of Clinical Laboratory, Maoming Hospital of Guangzhou University of Chinese Medicine, Maoming 525000, Guangdong, China; Corresponding author. Department of Laboratory Medicine, Shunde Hospital of Guangzhou University of Chinese Medicine, Foshan, China.
Background: A hyperinflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection gravely worsens the clinical progression of coronavirus disease 2019 (COVID-19). Although the undesirable effects of inflammasome activation have been correlated to the severity of COVID-19, the mechanisms of this process in the asymptomatic infection and disease progression have not yet been clearly elucidated. Methods: We performed strand-specific RNA sequencing in 39 peripheral blood mononuclear cell (PBMC) samples from asymptomatic individuals（n = 10）, symptomatic patients（n = 16） and healthy donors（n = 13）. Results: Dysregulation of pyrin inflammasomes along with the proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) gene was identified in SARS-COV-2 infection. Notably, the PSTPIP1 expression level showed a significant negative correlation with an adjacent long-noncoding RNA (lncRNA) RP11-797A18.6 in the asymptomatic individuals compared with the healthy controls. In addition, a decline in the nuclear factor kappa B subunit 1 (NFKB1) gene expression was observed in asymptomatic infection, followed by a rise in the mild and moderate disease stages, suggesting that altered NFKB1 expression and associated proinflammatory signals may trigger a disease progression. Conclusions: Overall, our results indicate that PSTPIP1-dependent pyrin inflammasomes-mediated pyroptosis and NF-κB activation might be potential preventive targets for COVID-19 disease development and progression.
