Innate immune responsiveness predicts both enhanced cellular immunity and symptomatic disease after controlled human influenza infection
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Controlled human influenza infection studies can uniquely interrogate the early immune factors associated with clinical outcome. Here, 27 healthy volunteers with low strain-specific serum neutralising antibody levels were challenged with influenza A/H3N2 virus. Twenty-two became infected, with 18 developing mild-moderate symptoms while 4 remained asymptomatic. Local and systemic immune profiling revealed innate pathways that engaged more rapidly and to a higher level in symptomatic individuals. Earlier monocyte and dendritic cell activation correlated with higher symptom scores but also enhanced natural killer (NK) and CD8+ T cell activation thereafter. At baseline, peripheral blood mononuclear cells (PBMCs) from symptomatics 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.
Date Issued
2026-07-01
Date Acceptance
2026-04-03
Citation
Nature Medicine, 2026, 32, pp.2556-2569
ISSN
1078-8956
Publisher
Nature Research
Start Page
2556
End Page
2569
Journal / Book Title
Nature Medicine
Volume
32
Issue
1
Copyright Statement
© The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
10.1038/s41591-026-04483-7
Publication Status
Published
Date Publish Online
2026-07-01