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<p>Plasmacytoid dendritic cells (pDCs) mount powerful antiviral type I interferon (IFN-I) responses, yet only a fraction of pDCs produces high levels of IFN-I. Here we report that peripheral pDCs in naive mice comprise three subsets (termed A, B and C) that represent progressive differentiation stages. This heterogeneity was generated by tonic IFN-I signaling elicited in part by the cGAS/STING and TLR9 DNA-sensing pathways. A small ‘IFN-I-naive’ subset (pDC-A) could give rise to other subsets; it was expanded in STING deficiency or after the IFN-I receptor blockade, but was abolished by exogenous IFN-I. In response to RNA viruses, pDC-A showed increased Bcl2-dependent survival and superior IFN-I responses, but was susceptible to virus infection. Conversely, the majority of pDCs comprised the ‘IFN-I-primed’ subsets (pDC-B/C) that showed lower IFN-I responses and poor survival, but did not support virus replication. Thus, tonic IFN-I signaling decreases the cytokine-producing capacity and survival of pDCs but increases their virus resistance, facilitating optimal antiviral responses.</p>

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Tonic type I interferon signaling optimizes the antiviral function of plasmacytoid dendritic cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月14日

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  • Joseph N. Pucella,
  • Raul A. Maqueda-Alfaro,
  • Hai Ni,
  • Fernando Bandeira Sulczewski,
  • Anna Eichinger,
  • Eduardo Esteva,
  • Ai C. Ra,
  • Annesa Das,
  • Oriana A. Perez,
  • Jue Feng,
  • Marlon Stoeckius,
  • Peter Smibert,
  • Alireza Khodadadi-Jamayran,
  • Igor Dolgalev,
  • Ellie Ivanova,
  • Stela Sota,
  • Ken Cadwell,
  • Sergei B. Koralov,
  • Judy Zhong,
  • Chetna Soni,
  • Daniel B. Stetson,
  • Stuart P. Weisberg,
  • Donna L. Farber,
  • Juliana Idoyaga,
  • Boris Reizis

摘要

Plasmacytoid dendritic cells (pDCs) mount powerful antiviral type I interferon (IFN-I) responses, yet only a fraction of pDCs produces high levels of IFN-I. Here we report that peripheral pDCs in naive mice comprise three subsets (termed A, B and C) that represent progressive differentiation stages. This heterogeneity was generated by tonic IFN-I signaling elicited in part by the cGAS/STING and TLR9 DNA-sensing pathways. A small ‘IFN-I-naive’ subset (pDC-A) could give rise to other subsets; it was expanded in STING deficiency or after the IFN-I receptor blockade, but was abolished by exogenous IFN-I. In response to RNA viruses, pDC-A showed increased Bcl2-dependent survival and superior IFN-I responses, but was susceptible to virus infection. Conversely, the majority of pDCs comprised the ‘IFN-I-primed’ subsets (pDC-B/C) that showed lower IFN-I responses and poor survival, but did not support virus replication. Thus, tonic IFN-I signaling decreases the cytokine-producing capacity and survival of pDCs but increases their virus resistance, facilitating optimal antiviral responses.