tetano
Editor, Senior Moderator
Nat Med
. 2026 Jul 1.
doi: 10.1038/s41591-026-04483-7. Online ahead of print.
Innate immune responsiveness predicts enhanced cellular immunity and symptomatic disease after controlled human influenza infection
Loukas Papargyris[SUP] 1 [/SUP], Jiayun Xu[SUP] 1 [/SUP], Claire Broderick[SUP] 1 [/SUP], Ao Huang[SUP] 2 3 [/SUP], Trupti Gore[SUP] 4 [/SUP], Arnold Reynaldi[SUP] 5 [/SUP], Pete Dayananda[SUP] 1 [/SUP], Ashley M Collins[SUP] 1 [/SUP], Stephanie Ascough[SUP] 1 [/SUP], Nathan Wong[SUP] 1 [/SUP], Jon Guy[SUP] 1 [/SUP], Jihye Song[SUP] 1 [/SUP], Satwik Kar[SUP] 1 [/SUP], Emma Bergstrom[SUP] 1 [/SUP], Lydia Slater[SUP] 1 [/SUP], Zoe Gardener[SUP] 1 [/SUP], Suzanna Paterson[SUP] 1 [/SUP], Mahdi Moradi Marjaneh[SUP] 1 [/SUP], Samuel J Nichols[SUP] 1 [/SUP], Victoria J Wright[SUP] 1 [/SUP], Min Kyu Park[SUP] 1 [/SUP], Richard McKendry[SUP] 1 [/SUP], Brad Nicholson[SUP] 6 [/SUP], Micah McClain[SUP] 6 [/SUP], Thomas W Burke[SUP] 6 [/SUP], Helen Wagstaffe[SUP] 1 [/SUP], Jelle Klein[SUP] 7 [/SUP], Michael Levin[SUP] 1 [/SUP], Alba Grifoni[SUP] 8 [/SUP], Christopher W Woods[SUP] 6 [/SUP], Miles P Davenport[SUP] 5 [/SUP], John S Tsang[SUP] 2 3 9 [/SUP], Benny Chain[SUP] 4 10 [/SUP], Myrsini Kaforou[SUP] 1 [/SUP], Christopher Chiu[SUP] 11 [/SUP]
Affiliations
Controlled human influenza infection studies can uniquely interrogate the early immune factors associated with clinical outcome. In this study, 27 healthy volunteers with low strain-specific serum neutralizing antibody levels were challenged with influenza A/H3N2 virus. Twenty-two became infected, with 18 developing mild-to-moderate symptoms and four remaining asymptomatic. Local and systemic immune profiling revealed innate pathways that engaged more rapidly and to a higher level in symptomatic participants. Earlier monocyte and dendritic cell activation correlated with higher symptom scores but also enhanced natural killer and CD8[SUP]+[/SUP] T cell activation thereafter. At baseline, peripheral blood mononuclear cells from symptomatic participants were more responsive to in vitro challenge, indicating a predisposition to divergent immunological outcomes at the time of virus exposure that was subsequently modulated by infection. These results show that human innate cell responsiveness is a predeterminant of both symptomatic disease and cellular immune responses known to promote viral clearance, suggesting potential targets for therapeutic intervention if decoupled.
. 2026 Jul 1.
doi: 10.1038/s41591-026-04483-7. Online ahead of print.
Innate immune responsiveness predicts enhanced cellular immunity and symptomatic disease after controlled human influenza infection
Loukas Papargyris[SUP] 1 [/SUP], Jiayun Xu[SUP] 1 [/SUP], Claire Broderick[SUP] 1 [/SUP], Ao Huang[SUP] 2 3 [/SUP], Trupti Gore[SUP] 4 [/SUP], Arnold Reynaldi[SUP] 5 [/SUP], Pete Dayananda[SUP] 1 [/SUP], Ashley M Collins[SUP] 1 [/SUP], Stephanie Ascough[SUP] 1 [/SUP], Nathan Wong[SUP] 1 [/SUP], Jon Guy[SUP] 1 [/SUP], Jihye Song[SUP] 1 [/SUP], Satwik Kar[SUP] 1 [/SUP], Emma Bergstrom[SUP] 1 [/SUP], Lydia Slater[SUP] 1 [/SUP], Zoe Gardener[SUP] 1 [/SUP], Suzanna Paterson[SUP] 1 [/SUP], Mahdi Moradi Marjaneh[SUP] 1 [/SUP], Samuel J Nichols[SUP] 1 [/SUP], Victoria J Wright[SUP] 1 [/SUP], Min Kyu Park[SUP] 1 [/SUP], Richard McKendry[SUP] 1 [/SUP], Brad Nicholson[SUP] 6 [/SUP], Micah McClain[SUP] 6 [/SUP], Thomas W Burke[SUP] 6 [/SUP], Helen Wagstaffe[SUP] 1 [/SUP], Jelle Klein[SUP] 7 [/SUP], Michael Levin[SUP] 1 [/SUP], Alba Grifoni[SUP] 8 [/SUP], Christopher W Woods[SUP] 6 [/SUP], Miles P Davenport[SUP] 5 [/SUP], John S Tsang[SUP] 2 3 9 [/SUP], Benny Chain[SUP] 4 10 [/SUP], Myrsini Kaforou[SUP] 1 [/SUP], Christopher Chiu[SUP] 11 [/SUP]
Affiliations
- PMID: 42387215
- DOI: 10.1038/s41591-026-04483-7
Controlled human influenza infection studies can uniquely interrogate the early immune factors associated with clinical outcome. In this study, 27 healthy volunteers with low strain-specific serum neutralizing antibody levels were challenged with influenza A/H3N2 virus. Twenty-two became infected, with 18 developing mild-to-moderate symptoms and four remaining asymptomatic. Local and systemic immune profiling revealed innate pathways that engaged more rapidly and to a higher level in symptomatic participants. Earlier monocyte and dendritic cell activation correlated with higher symptom scores but also enhanced natural killer and CD8[SUP]+[/SUP] T cell activation thereafter. At baseline, peripheral blood mononuclear cells from symptomatic participants were more responsive to in vitro challenge, indicating a predisposition to divergent immunological outcomes at the time of virus exposure that was subsequently modulated by infection. These results show that human innate cell responsiveness is a predeterminant of both symptomatic disease and cellular immune responses known to promote viral clearance, suggesting potential targets for therapeutic intervention if decoupled.