biostudies-literatureCole SLMedical Research CouncilThe Francis Crick InstituteNational Institute for Health Research (NIHR)Wellcome Truste91868https://www.ebi.ac.uk/biostudies/studies/S-EPMC5374077biostudies-literatureUnknown2(7)In each influenza season, a distinct group of young, otherwise healthy individuals with no risk factors succumbs to life-threatening infection. To better understand the cause for this, we analyzed a broad range of immune responses in blood from a unique cohort of patients, comprising previously healthy individuals hospitalized with and without respiratory failure during one influenza season, and infected with one specific influenza A strain. This analysis was compared with similarly hospitalized influenza patients with known risk factors (total of <i>n</i> = 60 patients recruited). We found a sustained increase in a specific subset of proinflammatory monocytes, with high TNF-α expression and an M1-like phenotype (independent of viral titers), in these previously healthy patients with severJCI insightM1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza.PMC5374077MC_U117512723G1001046MC_U117585868MC_G100121210030G1000758B090382/Z/09/ZMC_UU_12010/1MR/L018942/1NF-SI-0513-10150G0600520MC_UU_00008/1G1000758G0600371MR/R502121/1Dong TOpenshaw PJThomas CKok WLBenam KHBarclay WDrumright LMcCauley JLiew FYTaylor SBennett MPowell TJDunning JMartinez FOMcMichael AJHo LPBenlahrech ACerundolo VZambon MRepapi EMOSAIC investigatorsCole SLElderfield RfalseM1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza.In each influenza season, a distinct group of young, otherwise healthy individuals with no risk factors succumbs to life-threatening infection. To better understand the cause for this, we analyzed a broad range of immune responses in blood from a unique cohort of patients, comprising previously healthy individuals hospitalized with and without respiratory failure during one influenza season, and infected with one specific influenza A strain. This analysis was compared with similarly hospitalized influenza patients with known risk factors (total of <i>n</i> = 60 patients recruited). We found a sustained increase in a specific subset of proinflammatory monocytes, with high TNF-α expression and an M1-like phenotype (independent of viral titers), in these previously healthy patients with sever2017-01-01T00:00:00Z2017 Apr2026-05-30T13:45:10.155Z2019-03-27T02:39:58ZS-EPMC53740772840562210.1172/jci.insight.91868