tetano
Editor, Senior Moderator
Front Immunol
. 2022 Jan 14;12:799558.
doi: 10.3389/fimmu.2021.799558. eCollection 2021.
Persistent Oxidative Stress and Inflammasome Activation in CD14 [SUP]high[/SUP] CD16 [SUP]-[/SUP] Monocytes From COVID-19 Patients
Silvia Lucena Lage[SUP] 1 [/SUP], Eduardo Pinheiro Amaral[SUP] 2 [/SUP], Kerry L Hilligan[SUP] 2 3 [/SUP], Elizabeth Laidlaw[SUP] 1 [/SUP], Adam Rupert[SUP] 4 [/SUP], Sivaranjani Namasivayan[SUP] 2 [/SUP], Joseph Rocco[SUP] 1 [/SUP], Frances Galindo[SUP] 1 [/SUP], Anela Kellogg[SUP] 5 [/SUP], Princy Kumar[SUP] 6 [/SUP], Rita Poon[SUP] 7 [/SUP], Glenn W Wortmann[SUP] 8 [/SUP], John P Shannon[SUP] 9 [/SUP], Heather D Hickman[SUP] 9 [/SUP], Andrea Lisco[SUP] 1 [/SUP], Maura Manion[SUP] 1 [/SUP], Alan Sher[SUP] 2 [/SUP], Irini Sereti[SUP] 1 [/SUP]
Affiliations
Abstract
The poor outcome of the coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, is associated with systemic hyperinflammatory response and immunopathology. Although inflammasome and oxidative stress have independently been implicated in COVID-19, it is poorly understood whether these two pathways cooperatively contribute to disease severity. Herein, we found an enrichment of CD14[SUP]high[/SUP]CD16[SUP]-[/SUP] monocytes displaying inflammasome activation evidenced by caspase-1/ASC-speck formation in severe COVID-19 patients when compared to mild ones and healthy controls, respectively. Those cells also showed aberrant levels of mitochondrial superoxide and lipid peroxidation, both hallmarks of the oxidative stress response, which strongly correlated with caspase-1 activity. In addition, we found that NLRP3 inflammasome-derived IL-1β secretion by SARS-CoV-2-exposed monocytes in vitro was partially dependent on lipid peroxidation. Importantly, altered inflammasome and stress responses persisted after short-term patient recovery. Collectively, our findings suggest oxidative stress/NLRP3 signaling pathway as a potential target for host-directed therapy to mitigate early COVID-19 hyperinflammation and also its long-term outcomes.
Keywords: CD14highCD16− monocytes; COVID-19; NLRP3 inflammasome; lipid peroxidation; oxidative stress.
. 2022 Jan 14;12:799558.
doi: 10.3389/fimmu.2021.799558. eCollection 2021.
Persistent Oxidative Stress and Inflammasome Activation in CD14 [SUP]high[/SUP] CD16 [SUP]-[/SUP] Monocytes From COVID-19 Patients
Silvia Lucena Lage[SUP] 1 [/SUP], Eduardo Pinheiro Amaral[SUP] 2 [/SUP], Kerry L Hilligan[SUP] 2 3 [/SUP], Elizabeth Laidlaw[SUP] 1 [/SUP], Adam Rupert[SUP] 4 [/SUP], Sivaranjani Namasivayan[SUP] 2 [/SUP], Joseph Rocco[SUP] 1 [/SUP], Frances Galindo[SUP] 1 [/SUP], Anela Kellogg[SUP] 5 [/SUP], Princy Kumar[SUP] 6 [/SUP], Rita Poon[SUP] 7 [/SUP], Glenn W Wortmann[SUP] 8 [/SUP], John P Shannon[SUP] 9 [/SUP], Heather D Hickman[SUP] 9 [/SUP], Andrea Lisco[SUP] 1 [/SUP], Maura Manion[SUP] 1 [/SUP], Alan Sher[SUP] 2 [/SUP], Irini Sereti[SUP] 1 [/SUP]
Affiliations
- PMID: 35095880
- PMCID: PMC8795739
- DOI: 10.3389/fimmu.2021.799558
Abstract
The poor outcome of the coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, is associated with systemic hyperinflammatory response and immunopathology. Although inflammasome and oxidative stress have independently been implicated in COVID-19, it is poorly understood whether these two pathways cooperatively contribute to disease severity. Herein, we found an enrichment of CD14[SUP]high[/SUP]CD16[SUP]-[/SUP] monocytes displaying inflammasome activation evidenced by caspase-1/ASC-speck formation in severe COVID-19 patients when compared to mild ones and healthy controls, respectively. Those cells also showed aberrant levels of mitochondrial superoxide and lipid peroxidation, both hallmarks of the oxidative stress response, which strongly correlated with caspase-1 activity. In addition, we found that NLRP3 inflammasome-derived IL-1β secretion by SARS-CoV-2-exposed monocytes in vitro was partially dependent on lipid peroxidation. Importantly, altered inflammasome and stress responses persisted after short-term patient recovery. Collectively, our findings suggest oxidative stress/NLRP3 signaling pathway as a potential target for host-directed therapy to mitigate early COVID-19 hyperinflammation and also its long-term outcomes.
Keywords: CD14highCD16− monocytes; COVID-19; NLRP3 inflammasome; lipid peroxidation; oxidative stress.