tetano
Editor, Senior Moderator
Nat Commun. 2019 Jul 31;10(1):3422. doi: 10.1038/s41467-019-11249-y.
[h=1]Neutrophils-related host factors associated with severe disease and fatality in patients with influenza infection.[/h] Tang BM[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Shojaei M[SUP]4,[/SUP][SUP]5[/SUP], Teoh S[SUP]4[/SUP], Meyers A[SUP]6[/SUP], Ho J[SUP]6[/SUP], Ball TB[SUP]6[/SUP], Keynan Y[SUP]7[/SUP], Pisipati A[SUP]8[/SUP], Kumar A[SUP]9[/SUP], Eisen DP[SUP]10[/SUP], Lai K[SUP]11[/SUP], Gillett M[SUP]12[/SUP], Santram R[SUP]13[/SUP], Geffers R[SUP]14[/SUP], Schreiber J[SUP]15[/SUP], Mozhui K[SUP]16[/SUP], Huang S[SUP]4[/SUP], Parnell GP[SUP]5[/SUP], Nalos M[SUP]4,[/SUP][SUP]17[/SUP], Holubova M[SUP]18[/SUP], Chew T[SUP]19[/SUP], Booth D[SUP]5[/SUP], Kumar A[SUP]20[/SUP], McLean A[SUP]4[/SUP], Schughart K[SUP]21,[/SUP][SUP]22,[/SUP][SUP]23[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Severe influenza infection has no effective treatment available. One of the key barriers to developing host-directed therapy is a lack of reliable prognostic factors needed to guide such therapy. Here, we use a network analysis approach to identify host factors associated with severe influenza and fatal outcome. In influenza patients with moderate-to-severe diseases, we uncover a complex landscape of immunological pathways, with the main changes occurring in pathways related to circulating neutrophils. Patients with severe disease display excessive neutrophil extracellular traps formation, neutrophil-inflammation and delayed apoptosis, all of which have been associated with fatal outcome in animal models. Excessive neutrophil activation correlates with worsening oxygenation impairment and predicted fatal outcome (AUROC 0.817-0.898). These findings provide new evidence that neutrophil-dominated host response is associated with poor outcomes. Measuring neutrophil-related changes may improve risk stratification and patient selection, a critical first step in developing host-directed immune therapy.
PMID: 31366921 DOI: 10.1038/s41467-019-11249-y
[h=1]Neutrophils-related host factors associated with severe disease and fatality in patients with influenza infection.[/h] Tang BM[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Shojaei M[SUP]4,[/SUP][SUP]5[/SUP], Teoh S[SUP]4[/SUP], Meyers A[SUP]6[/SUP], Ho J[SUP]6[/SUP], Ball TB[SUP]6[/SUP], Keynan Y[SUP]7[/SUP], Pisipati A[SUP]8[/SUP], Kumar A[SUP]9[/SUP], Eisen DP[SUP]10[/SUP], Lai K[SUP]11[/SUP], Gillett M[SUP]12[/SUP], Santram R[SUP]13[/SUP], Geffers R[SUP]14[/SUP], Schreiber J[SUP]15[/SUP], Mozhui K[SUP]16[/SUP], Huang S[SUP]4[/SUP], Parnell GP[SUP]5[/SUP], Nalos M[SUP]4,[/SUP][SUP]17[/SUP], Holubova M[SUP]18[/SUP], Chew T[SUP]19[/SUP], Booth D[SUP]5[/SUP], Kumar A[SUP]20[/SUP], McLean A[SUP]4[/SUP], Schughart K[SUP]21,[/SUP][SUP]22,[/SUP][SUP]23[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Severe influenza infection has no effective treatment available. One of the key barriers to developing host-directed therapy is a lack of reliable prognostic factors needed to guide such therapy. Here, we use a network analysis approach to identify host factors associated with severe influenza and fatal outcome. In influenza patients with moderate-to-severe diseases, we uncover a complex landscape of immunological pathways, with the main changes occurring in pathways related to circulating neutrophils. Patients with severe disease display excessive neutrophil extracellular traps formation, neutrophil-inflammation and delayed apoptosis, all of which have been associated with fatal outcome in animal models. Excessive neutrophil activation correlates with worsening oxygenation impairment and predicted fatal outcome (AUROC 0.817-0.898). These findings provide new evidence that neutrophil-dominated host response is associated with poor outcomes. Measuring neutrophil-related changes may improve risk stratification and patient selection, a critical first step in developing host-directed immune therapy.
PMID: 31366921 DOI: 10.1038/s41467-019-11249-y