tetano
Editor, Senior Moderator
JCI Insight
. 2024 Sep 10;9(17):e171659.
doi: 10.1172/jci.insight.171659. Emergence of dysfunctional neutrophils with a defect in arginase-1 release in severe COVID-19
Amrita Dwivedi[SUP] 1 [/SUP], Aisling Ui Mhaonaigh[SUP] 1 [/SUP], Makala Carroll[SUP] 1 [/SUP], Bahareh Khosravi[SUP] 1 [/SUP], Isabella Batten[SUP] 2 [/SUP], Robert Seán Ballantine[SUP] 1 [/SUP], Stuart Hendricken Phelan[SUP] 3 [/SUP], Laura O'Doherty[SUP] 3 4 [/SUP], Angel Mary George[SUP] 5 [/SUP], Jacklyn Sui[SUP] 2 5 [/SUP], Heike C Hawerkamp[SUP] 6 [/SUP], Padraic G Fallon[SUP] 6 7 [/SUP], Elnè Noppe[SUP] 8 [/SUP], Sabina Mason[SUP] 8 [/SUP], Niall Conlon[SUP] 4 5 [/SUP], Clíona Ni Cheallaigh[SUP] 4 [/SUP], Conor M Finlay[SUP] 1 [/SUP], Mark A Little[SUP] 1 [/SUP], On Behalf Of The St James's And Tallaght Trinity Allied Researchers Sttar Bioresource[SUP] 9 [/SUP]
Affiliations
Neutrophilia occurs in patients infected with SARS-CoV-2 (COVID-19) and is predictive of poor outcomes. Here, we link heterogenous neutrophil populations to disease severity in COVID-19. We identified neutrophils with features of cellular aging and immunosuppressive capacity in mild COVID-19 and features of neutrophil immaturity and activation in severe disease. The low-density neutrophil (LDN) number in circulating blood correlated with COVID-19 severity. Many of the divergent neutrophil phenotypes in COVID-19 were overrepresented in the LDN fraction and were less detectable in normal-density neutrophils. Functionally, neutrophils from patients with severe COVID-19 displayed defects in neutrophil extracellular trap formation and reactive oxygen species production. Soluble factors secreted by neutrophils from these patients inhibited T cell proliferation. Neutrophils from patients with severe COVID-19 had increased expression of arginase-1 protein, a feature that was retained in convalescent patients. Despite this increase in intracellular expression, there was a reduction in arginase-1 release by neutrophils into serum and culture supernatants. Furthermore, neutrophil-mediated T cell suppression was independent of arginase-1. Our results indicate the presence of dysfunctional, activated, and immature neutrophils in severe COVID-19.
Keywords: COVID-19; Immunology; Neutrophils.
. 2024 Sep 10;9(17):e171659.
doi: 10.1172/jci.insight.171659. Emergence of dysfunctional neutrophils with a defect in arginase-1 release in severe COVID-19
Amrita Dwivedi[SUP] 1 [/SUP], Aisling Ui Mhaonaigh[SUP] 1 [/SUP], Makala Carroll[SUP] 1 [/SUP], Bahareh Khosravi[SUP] 1 [/SUP], Isabella Batten[SUP] 2 [/SUP], Robert Seán Ballantine[SUP] 1 [/SUP], Stuart Hendricken Phelan[SUP] 3 [/SUP], Laura O'Doherty[SUP] 3 4 [/SUP], Angel Mary George[SUP] 5 [/SUP], Jacklyn Sui[SUP] 2 5 [/SUP], Heike C Hawerkamp[SUP] 6 [/SUP], Padraic G Fallon[SUP] 6 7 [/SUP], Elnè Noppe[SUP] 8 [/SUP], Sabina Mason[SUP] 8 [/SUP], Niall Conlon[SUP] 4 5 [/SUP], Clíona Ni Cheallaigh[SUP] 4 [/SUP], Conor M Finlay[SUP] 1 [/SUP], Mark A Little[SUP] 1 [/SUP], On Behalf Of The St James's And Tallaght Trinity Allied Researchers Sttar Bioresource[SUP] 9 [/SUP]
Affiliations
- PMID: 39253969
- DOI: 10.1172/jci.insight.171659
Neutrophilia occurs in patients infected with SARS-CoV-2 (COVID-19) and is predictive of poor outcomes. Here, we link heterogenous neutrophil populations to disease severity in COVID-19. We identified neutrophils with features of cellular aging and immunosuppressive capacity in mild COVID-19 and features of neutrophil immaturity and activation in severe disease. The low-density neutrophil (LDN) number in circulating blood correlated with COVID-19 severity. Many of the divergent neutrophil phenotypes in COVID-19 were overrepresented in the LDN fraction and were less detectable in normal-density neutrophils. Functionally, neutrophils from patients with severe COVID-19 displayed defects in neutrophil extracellular trap formation and reactive oxygen species production. Soluble factors secreted by neutrophils from these patients inhibited T cell proliferation. Neutrophils from patients with severe COVID-19 had increased expression of arginase-1 protein, a feature that was retained in convalescent patients. Despite this increase in intracellular expression, there was a reduction in arginase-1 release by neutrophils into serum and culture supernatants. Furthermore, neutrophil-mediated T cell suppression was independent of arginase-1. Our results indicate the presence of dysfunctional, activated, and immature neutrophils in severe COVID-19.
Keywords: COVID-19; Immunology; Neutrophils.