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<p>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.</p>

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Innate immune responsiveness predicts enhanced cellular immunity and symptomatic disease after controlled human influenza infection

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月1日

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  • Loukas Papargyris,
  • Jiayun Xu,
  • Claire Broderick,
  • Ao Huang,
  • Trupti Gore,
  • Arnold Reynaldi,
  • Pete Dayananda,
  • Ashley M. Collins,
  • Stephanie Ascough,
  • Nathan Wong,
  • Jon Guy,
  • Jihye Song,
  • Satwik Kar,
  • Emma Bergstrom,
  • Lydia Slater,
  • Zoe Gardener,
  • Suzanna Paterson,
  • Mahdi Moradi Marjaneh,
  • Samuel J. Nichols,
  • Victoria J. Wright,
  • Min Kyu Park,
  • Richard McKendry,
  • Brad Nicholson,
  • Micah McClain,
  • Thomas W. Burke,
  • Helen Wagstaffe,
  • Jelle Klein,
  • Michael Levin,
  • Alba Grifoni,
  • Christopher W. Woods,
  • Miles P. Davenport,
  • John S. Tsang,
  • Benny Chain,
  • Myrsini Kaforou,
  • Christopher Chiu

摘要

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+ 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.