NLRP12 Senses the SARS-CoV-2 Membrane Protein and Promotes an Inflammatory Response

Author:

Li Xingyu123,Zhou Guangde1,Sun Xingzi12,Qu Siying2,Lai Hongzhi4,Wu Yongjian2,Li Dechang5,Liu Lei1,Zhang Guoliang1,Yang Jingwen6,Huang Xi123ORCID

Affiliation:

1. National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology , Shenzhen

2. Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University , Zhuhai

3. Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou

4. The Third People's Hospital of Shantou, Shantou Medical Intensive Care Unit,

5. Tuberculosis Prevention and Control Institution, Yuebei Second People's Hospital , Shaoguan

6. Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University , Qingyuan , China

Abstract

Abstract COVID-19 is an acute respiratory disorder that is caused by SARS-CoV-2, in which excessive systemic inflammation is associated with adverse patient clinical outcomes. Here, we observed elevated expression levels of NLRP12 (nucleotide-binding leucine-rich repeat–containing receptor 12) in human peripheral monocytes and lung tissue during infection with SARS-CoV-2. Co-immunoprecipitation analysis revealed that NLRP12 directly interacted with the M protein through its leucine-rich repeat domain. Moreover, in vitro studies demonstrated that NLRP12 interacted with TRAF3 and promoted its ubiquitination and degradation, which counteracted the inhibitory effect of TRAF3 on the NF-κB/MAPK signaling pathway and promoted the production of inflammatory cytokines. Furthermore, an in vivo study revealed that NLRP12 knockout mice displayed attenuated tissue injury and ameliorated inflammatory responses in the lungs when infected with a SARS-CoV-2 M protein–reconstituted pseudovirus and mouse coronavirus. Taken together, these findings suggest that NLRP12 mediates the inflammatory responses during coronavirus infection.

Funder

National Natural Science Foundation of China

National Science and Technology Key Projects for Major Infectious Diseases

Development Project of Foshan Fourth People’s Hospital

Department of Science and Technology of Guangdong Province to the Guangdong Provincial Key Laboratory of Biomedical Imaging

Guangdong Medical Science and Technology Research Fund Project

Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital

Shenzhen High-level Hospital Construction Fund

Three Major Scientific Research Projects of Sun Yat-sen University

Guangdong Scientific and Technological Research Project for COVID-19

Zhuhai Scientific and Technological Research Project for COVID-19

Guangdong Science and Technology Special Fund Project

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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