Scholarlink

<p>Plasmacytoid dendritic cells (pDCs) are major producers of type I/III interferons. As interferons are crucial for antiviral defense, pDCs are assumed to play an essential role in this process; however, robust evidence supporting this dogma is scarce. Genetic or pharmacological manipulations that eliminate pDCs or disrupt their interferon production often affect other cells, confounding interpretation. Here, to overcome this issue, we engineered pDC-less mice that are specifically and constitutively devoid of pDCs by expressing diphtheria toxin under coordinated control of the <i>Siglech</i> and <i>Pacsin1</i> genes, uniquely coexpressed in pDCs. pDC-less mice mounted protective immunity against systemic infection with mouse cytomegalovirus and showed higher survival and less lung immunopathology to intranasal infection with influenza virus and SARS-CoV-2. Thus, contrary to the prevailing dogma, we revealed that pDCs and their interferons are dispensable or deleterious during several viral infections. pDC-less mice will enable rigorously reassessing the roles of pDCs in health and disease.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Plasmacytoid dendritic cells are dispensable or detrimental in murine systemic or respiratory viral infections

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年9月29日

查看全文
  • Clemence Ngo,
  • Camille Pierini-Malosse,
  • Khalissa Rahmani,
  • Michael Valente,
  • Nils Collinet,
  • Gilles Bessou,
  • Capucine Guerry,
  • Manon Fabregue,
  • Solene Mathieu,
  • Sarah Sharkaoui,
  • Sophie Mazzoli,
  • Amandine Sansoni,
  • Frederic Fiore,
  • Caroline Laprie,
  • Lena Alexopoulou,
  • Mauro Gaya,
  • Claude Gregoire,
  • Achille Broggi,
  • Sarah Wurbel,
  • Réjane Rua,
  • Narjess Haidar,
  • Pierre Milpied,
  • Bertrand Escalière,
  • Thien Phong Vu Manh,
  • Mathieu Fallet,
  • Lionel Chasson,
  • Hien Tran,
  • Thomas Baranek,
  • Marc Le Bert,
  • Bernard Malissen,
  • Ana Zarubica,
  • Marc Dalod,
  • Elena Tomasello

摘要

Plasmacytoid dendritic cells (pDCs) are major producers of type I/III interferons. As interferons are crucial for antiviral defense, pDCs are assumed to play an essential role in this process; however, robust evidence supporting this dogma is scarce. Genetic or pharmacological manipulations that eliminate pDCs or disrupt their interferon production often affect other cells, confounding interpretation. Here, to overcome this issue, we engineered pDC-less mice that are specifically and constitutively devoid of pDCs by expressing diphtheria toxin under coordinated control of the Siglech and Pacsin1 genes, uniquely coexpressed in pDCs. pDC-less mice mounted protective immunity against systemic infection with mouse cytomegalovirus and showed higher survival and less lung immunopathology to intranasal infection with influenza virus and SARS-CoV-2. Thus, contrary to the prevailing dogma, we revealed that pDCs and their interferons are dispensable or deleterious during several viral infections. pDC-less mice will enable rigorously reassessing the roles of pDCs in health and disease.