tetano
Editor, Senior Moderator
PLoS Pathog
. 2024 Aug 22;20(8):e1012368.
doi: 10.1371/journal.ppat.1012368. eCollection 2024 Aug. The assembly of neutrophil inflammasomes during COVID-19 is mediated by type I interferons
Luz E Cabrera[SUP] 1 [/SUP], Suvi T Jokiranta[SUP] 2 3 [/SUP], Sanna Mäki[SUP] 1 [/SUP], Simo Miettinen[SUP] 1 4 [/SUP], Ravi Kant[SUP] 1 4 5 [/SUP], Lauri Kareinen[SUP] 1 4 [/SUP], Tarja Sironen[SUP] 1 4 [/SUP], Jukka-Pekka Pietilä[SUP] 6 7 [/SUP], Anu Kantele[SUP] 6 7 [/SUP], Eliisa Kekäläinen[SUP] 2 3 8 [/SUP], Hanna Lindgren[SUP] 9 [/SUP], Pirkko Mattila[SUP] 9 [/SUP], Anja Kipar[SUP] 4 10 11 [/SUP], Olli Vapalahti[SUP] 1 4 8 [/SUP], Tomas Strandin[SUP] 1 [/SUP]
Affiliations
The severity of COVID-19 is linked to excessive inflammation. Neutrophils represent a critical arm of the innate immune response and are major mediators of inflammation, but their role in COVID-19 pathophysiology remains poorly understood. We conducted transcriptomic profiling of neutrophils obtained from patients with mild and severe COVID-19, as well as from SARS-CoV-2 infected mice, in comparison to non-infected healthy controls. In addition, we investigated the inflammasome formation potential in neutrophils from patients and mice upon SARS-CoV-2 infection. Transcriptomic analysis of polymorphonuclear cells (PMNs), consisting mainly of mature neutrophils, revealed a striking type I interferon (IFN-I) gene signature in severe COVID-19 patients, contrasting with mild COVID-19 and healthy controls. Notably, low-density granulocytes (LDGs) from severe COVID-19 patients exhibited an immature neutrophil phenotype and lacked this IFN-I signature. Moreover, PMNs from severe COVID-19 patients showed heightened nigericin-induced caspase1 activation, but reduced responsiveness to exogenous inflammasome priming. Furthermore, IFN-I emerged as a priming stimulus for neutrophil inflammasomes. These findings suggest a potential role for neutrophil inflammasomes in driving inflammation during severe COVID-19. Altogether, these findings open promising avenues for targeted therapeutic interventions to mitigate the pathological processes associated with the disease.
. 2024 Aug 22;20(8):e1012368.
doi: 10.1371/journal.ppat.1012368. eCollection 2024 Aug. The assembly of neutrophil inflammasomes during COVID-19 is mediated by type I interferons
Luz E Cabrera[SUP] 1 [/SUP], Suvi T Jokiranta[SUP] 2 3 [/SUP], Sanna Mäki[SUP] 1 [/SUP], Simo Miettinen[SUP] 1 4 [/SUP], Ravi Kant[SUP] 1 4 5 [/SUP], Lauri Kareinen[SUP] 1 4 [/SUP], Tarja Sironen[SUP] 1 4 [/SUP], Jukka-Pekka Pietilä[SUP] 6 7 [/SUP], Anu Kantele[SUP] 6 7 [/SUP], Eliisa Kekäläinen[SUP] 2 3 8 [/SUP], Hanna Lindgren[SUP] 9 [/SUP], Pirkko Mattila[SUP] 9 [/SUP], Anja Kipar[SUP] 4 10 11 [/SUP], Olli Vapalahti[SUP] 1 4 8 [/SUP], Tomas Strandin[SUP] 1 [/SUP]
Affiliations
- PMID: 39172744
- DOI: 10.1371/journal.ppat.1012368
The severity of COVID-19 is linked to excessive inflammation. Neutrophils represent a critical arm of the innate immune response and are major mediators of inflammation, but their role in COVID-19 pathophysiology remains poorly understood. We conducted transcriptomic profiling of neutrophils obtained from patients with mild and severe COVID-19, as well as from SARS-CoV-2 infected mice, in comparison to non-infected healthy controls. In addition, we investigated the inflammasome formation potential in neutrophils from patients and mice upon SARS-CoV-2 infection. Transcriptomic analysis of polymorphonuclear cells (PMNs), consisting mainly of mature neutrophils, revealed a striking type I interferon (IFN-I) gene signature in severe COVID-19 patients, contrasting with mild COVID-19 and healthy controls. Notably, low-density granulocytes (LDGs) from severe COVID-19 patients exhibited an immature neutrophil phenotype and lacked this IFN-I signature. Moreover, PMNs from severe COVID-19 patients showed heightened nigericin-induced caspase1 activation, but reduced responsiveness to exogenous inflammasome priming. Furthermore, IFN-I emerged as a priming stimulus for neutrophil inflammasomes. These findings suggest a potential role for neutrophil inflammasomes in driving inflammation during severe COVID-19. Altogether, these findings open promising avenues for targeted therapeutic interventions to mitigate the pathological processes associated with the disease.