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<p>T-cell activation is a key feature of chronic HIV infection and is predictive of non-AIDS-defining comorbidities in people with HIV (PWH) receiving antiretroviral therapy (ART). Monocytes from PWH display distinct transcriptional programs, yet their role in T-cell activation remains unclear. In this study, we investigated how the response of CD14<sup>+</sup> monocytes from PWH to type I interferon (IFN-I) influences T-cell activation. Ex vivo transcriptional profiles and in vitro IFN-I responses of CD14<sup>+</sup> monocytes were compared between PWH and uninfected individuals (UI). We identified distinct ex vivo transcriptional signatures in CD14<sup>+</sup> monocytes from PWH versus UI, as well as differential responses to IFN-I. T cells from ART-treated PWH exhibited persistent activation, which correlated positively with IFN-I-stimulated gene expression. In vitro IFN-I exposure led to increased proportions of activated CD4<sup>+</sup> T cells in PWH - but not in UI – under conditions of TCR engagement, an effect reproduced by the transfer of IFN-I-primed CD14<sup>+</sup> monocytes. Finally, JAK inhibitors effectively blocked IFN-I-mediated T-cell activation. Our findings underscore the role of IFN-I-primed CD14<sup>+</sup> monocytes in sustaining chronic T-cell activation during HIV infection and highlight JAK inhibitors as a potential therapeutic strategy.</p>

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Type I interferon responses in CD14+ monocytes amplify CD4+ T-cell activation in PWH

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月28日

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  • Léo Plaçais,
  • Béatrice Jacquelin,
  • Marion Camard,
  • Martin Dutertre,
  • Vanessa d’Urbano,
  • Annamaria Paolini,
  • Marie Bitu,
  • Christelliah Mouanga,
  • Oscar Haigh,
  • Katia Bourdic,
  • Delphine Desjardins,
  • Michaela Müller-Trutwin,
  • Christine Bourgeois,
  • Olivier Lambotte,
  • Nicolas Noel

摘要

T-cell activation is a key feature of chronic HIV infection and is predictive of non-AIDS-defining comorbidities in people with HIV (PWH) receiving antiretroviral therapy (ART). Monocytes from PWH display distinct transcriptional programs, yet their role in T-cell activation remains unclear. In this study, we investigated how the response of CD14+ monocytes from PWH to type I interferon (IFN-I) influences T-cell activation. Ex vivo transcriptional profiles and in vitro IFN-I responses of CD14+ monocytes were compared between PWH and uninfected individuals (UI). We identified distinct ex vivo transcriptional signatures in CD14+ monocytes from PWH versus UI, as well as differential responses to IFN-I. T cells from ART-treated PWH exhibited persistent activation, which correlated positively with IFN-I-stimulated gene expression. In vitro IFN-I exposure led to increased proportions of activated CD4+ T cells in PWH - but not in UI – under conditions of TCR engagement, an effect reproduced by the transfer of IFN-I-primed CD14+ monocytes. Finally, JAK inhibitors effectively blocked IFN-I-mediated T-cell activation. Our findings underscore the role of IFN-I-primed CD14+ monocytes in sustaining chronic T-cell activation during HIV infection and highlight JAK inhibitors as a potential therapeutic strategy.