tetano
Editor, Senior Moderator
Int Immunopharmacol
. 2023 Feb 27;117:109954.
doi: 10.1016/j.intimp.2023.109954. Online ahead of print.
SARS-CoV-2 immune complex triggers human monocyte necroptosis
Leonardo Duarte Santos[SUP] 1 [/SUP], Krist Helen Antunes[SUP] 1 [/SUP], Gisele Cassão[SUP] 1 [/SUP], João Ismael Gonçalves[SUP] 1 [/SUP], Bruno Lopes Abbadi[SUP] 2 [/SUP], Cristiano Valim Bizarro[SUP] 2 [/SUP], Luiz Augusto Basso[SUP] 2 [/SUP], Pablo Machado[SUP] 2 [/SUP], Ana Paula D de Souza[SUP] 3 [/SUP], Bárbara Nery Porto[SUP] 4 [/SUP]
Affiliations
Abstract
We analyzed the ability of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) itself and SARS-CoV-2-IgG immune complexes to trigger human monocyte necroptosis. SARS-CoV-2 was able to induce monocyte necroptosis dependently of MLKL activation. Necroptosis-associated proteins (RIPK1, RIPK3 and MLKL) were involved in SARS-CoV-2N1 gene expression in monocytes. SARS-CoV-2 immune complexes promoted monocyte necroptosis in a RIPK3- and MLKL-dependent manner, and Syk tyrosine kinase was necessary for SARS-CoV-2 immune complex-induced monocyte necroptosis, indicating the involvement of Fcγ receptors on necroptosis. Finally, we provide evidence that elevated LDH levels as a marker of lytic cell death are associated with COVID-19 pathogenesis.
Keywords: COVD-19 pathogenesis; Fcγ receptors; MLKL; Monocyte; Necroptosis; SARS-CoV-2.
. 2023 Feb 27;117:109954.
doi: 10.1016/j.intimp.2023.109954. Online ahead of print.
SARS-CoV-2 immune complex triggers human monocyte necroptosis
Leonardo Duarte Santos[SUP] 1 [/SUP], Krist Helen Antunes[SUP] 1 [/SUP], Gisele Cassão[SUP] 1 [/SUP], João Ismael Gonçalves[SUP] 1 [/SUP], Bruno Lopes Abbadi[SUP] 2 [/SUP], Cristiano Valim Bizarro[SUP] 2 [/SUP], Luiz Augusto Basso[SUP] 2 [/SUP], Pablo Machado[SUP] 2 [/SUP], Ana Paula D de Souza[SUP] 3 [/SUP], Bárbara Nery Porto[SUP] 4 [/SUP]
Affiliations
- PMID: 36870284
- DOI: 10.1016/j.intimp.2023.109954
Abstract
We analyzed the ability of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) itself and SARS-CoV-2-IgG immune complexes to trigger human monocyte necroptosis. SARS-CoV-2 was able to induce monocyte necroptosis dependently of MLKL activation. Necroptosis-associated proteins (RIPK1, RIPK3 and MLKL) were involved in SARS-CoV-2N1 gene expression in monocytes. SARS-CoV-2 immune complexes promoted monocyte necroptosis in a RIPK3- and MLKL-dependent manner, and Syk tyrosine kinase was necessary for SARS-CoV-2 immune complex-induced monocyte necroptosis, indicating the involvement of Fcγ receptors on necroptosis. Finally, we provide evidence that elevated LDH levels as a marker of lytic cell death are associated with COVID-19 pathogenesis.
Keywords: COVD-19 pathogenesis; Fcγ receptors; MLKL; Monocyte; Necroptosis; SARS-CoV-2.