Abstract

A cytokine storm induces acute respiratory distress syndrome, the main cause of death in coronavirus disease 2019 (COVID-19) patients. However, the detailed mechanisms of cytokine induction due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain unclear. To examine the cytokine production in COVID-19, we mimicked the disease in SARS-CoV-2-infected alveoli by adding the lysate of SARS-CoV-2-infected cells to cultured macrophages or induced pluripotent stem cell-derived myeloid cells. The cells secreted interleukin (IL)-6 after the addition of SARS-CoV-2-infected cell lysate. Screening of 25 SARS-CoV-2 protein-expressing plasmids revealed that the N protein-coding plasmid alone induced IL-6 production. The addition of anti-N antibody further enhanced IL-6 production, but the F(ab’)2 fragment did not. Sera from COVID-19 patients also enhanced IL-6 production, and sera from patients with severer disease induced higher levels of IL-6. These results suggest that anti-N antibody promotes IL-6 production in SARS-CoV-2-infected alveoli, leading to the cytokine storm of COVID-19.

Details

Title
Anti-nucleocapsid antibodies enhance the production of IL-6 induced by SARS-CoV-2 N protein
Author
Nakayama, Emi E 1 ; Kubota-Koketsu Ritsuko 1 ; Sasaki Tadahiro 1 ; Suzuki, Keita 2 ; Uno Kazuko 3 ; Shimizu, Jun 4 ; Okamoto Toru 5 ; Matsumoto Hisatake 6 ; Matsuura, Hiroshi 7 ; Hashimoto Shoji 8 ; Tanaka, Toshio 8 ; Harada Hiromasa 9 ; Tomita Masafumi 10 ; Kaneko Mitsunori 11 ; Yoshizaki Kazuyuki 12 ; Shioda Tatsuo 1 

 Osaka University, Research Institute for Microbial Diseases and Center for Infectious Disease Education and Research, Suita, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971) 
 Osaka University, Research Institute for Microbial Diseases and Center for Infectious Disease Education and Research, Suita, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971); TANAKA Kikinzoku Kogyo K.K, Hiratsuka, Japan (GRID:grid.480415.c) 
 Louis Pasteur Center for Medical Research, Division of Basic Research, Kyoto, Japan (GRID:grid.452539.c) (ISNI:0000 0004 0621 0957) 
 MiCAN Technologies Inc., Kyoto, Japan (GRID:grid.452539.c) 
 Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971) 
 Osaka University, Trauma and Acute Critical Care Center, Suita, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971) 
 Osaka Prefectural Nakakawachi Emergency and Critical Care Center, Higashiosaka, Osaka, Japan (GRID:grid.136593.b) 
 Osaka Prefectural Hospital Organization Osaka Habikino Medical Center, Habikino, Osaka, Japan (GRID:grid.416985.7) (ISNI:0000 0004 0378 3952) 
 Yao Tokushukai General Hospital, Yao, Osaka, Japan (GRID:grid.417339.b) 
10  Kobe Tokushukai Hospital, Kobe, Japan (GRID:grid.417339.b) 
11  Suita Tokushukai Hospital, Suita, Osaka, Japan (GRID:grid.459995.d) (ISNI:0000 0004 4682 8284) 
12  Osaka University, Institute of Scientific and Industry Research, Ibaraki, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2664960219
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.