Anti-nucleocapsid antibodies enhance the production of IL-6 induced by SARS-CoV-2 N protein

• Published in: Scientific reports Vol. 12; no. 1; pp. 8108 - 13
• Main Authors: Nakayama, Emi E., Kubota-Koketsu, Ritsuko, Sasaki, Tadahiro, Suzuki, Keita, Uno, Kazuko, Shimizu, Jun, Okamoto, Toru, Matsumoto, Hisatake, Matsuura, Hiroshi, Hashimoto, Shoji, Tanaka, Toshio, Harada, Hiromasa, Tomita, Masafumi, Kaneko, Mitsunori, Yoshizaki, Kazuyuki, Shioda, Tatsuo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.05.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250; 631/326; 692/420; 692/499; 692/699; Alveoli; Coronaviruses; COVID-19; Cytokine Release Syndrome; Cytokine storm; Cytokines; Humanities and Social Sciences; Humans; Interleukin 6; Macrophages; multidisciplinary; Myeloid cells; N protein; Nucleocapsids; Plasmids; Pluripotency; Proteins; Respiratory distress syndrome; SARS-CoV-2; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Stem cells
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-12252-y

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.