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<p>Natural killer (NK) cells play a key role in combating invasive mycoses, with surface proteins crucial for immune cell-target interactions. Here, we investigate the role of DNAX accessory molecule 1 (DNAM-1; CD226) in the recognition of <i>Aspergillus fumigatus</i> and <i>Candida albicans</i> hyphae. Super-resolution microscopy reveals a uniform distribution of DNAM-1 on naïve NK cells that is maintained upon contact with fungal hyphae. However, soluble DNAM-1 binds to the fungal cell wall and blocking DNAM-1 reduces antifungal activity in colony-forming assays. Furthermore, in silico domain–domain interaction analysis identifies several fungal proteins as putative DNAM-1 targets, including OpsB in <i>A. fumigatus</i> and Sap10 in <i>C. albicans</i>. High-affinity binding between Sap10 and DNAM-1 is predicted computationally and confirmed experimentally by co-immunoprecipitation and fluorescence correlation spectroscopy. Microscopic analysis further demonstrates that Sap10 binds to primary NK cells but not to DNAM-1-deficient NK cells. Sap10 binding induced NK-cell activation, as evidenced by increased CD69 expression and elevated perforin and CCL3 secretion. These findings identify Sap10 as a fungal ligand of DNAM-1 and reveal a mechanism by which NK cells recognize fungal pathogens.</p><p></p>

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DNAM-1 mediates NK-cell activation and host-pathogen interaction via direct binding to fungal cell wall proteases

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月13日

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  • Fariha Natasha,
  • Linda Heilig,
  • Dominic A. Helmerich,
  • Christian Luther,
  • Jan Springer,
  • Bipasa Kar,
  • Matthias Drobny,
  • Lydia Kasper,
  • Carla Schuh,
  • Marcus Dittrich,
  • Bernhard Hube,
  • Thomas Dandekar,
  • Markus Sauer,
  • Jürgen Löffler,
  • Ulrich Terpitz

摘要

Natural killer (NK) cells play a key role in combating invasive mycoses, with surface proteins crucial for immune cell-target interactions. Here, we investigate the role of DNAX accessory molecule 1 (DNAM-1; CD226) in the recognition of Aspergillus fumigatus and Candida albicans hyphae. Super-resolution microscopy reveals a uniform distribution of DNAM-1 on naïve NK cells that is maintained upon contact with fungal hyphae. However, soluble DNAM-1 binds to the fungal cell wall and blocking DNAM-1 reduces antifungal activity in colony-forming assays. Furthermore, in silico domain–domain interaction analysis identifies several fungal proteins as putative DNAM-1 targets, including OpsB in A. fumigatus and Sap10 in C. albicans. High-affinity binding between Sap10 and DNAM-1 is predicted computationally and confirmed experimentally by co-immunoprecipitation and fluorescence correlation spectroscopy. Microscopic analysis further demonstrates that Sap10 binds to primary NK cells but not to DNAM-1-deficient NK cells. Sap10 binding induced NK-cell activation, as evidenced by increased CD69 expression and elevated perforin and CCL3 secretion. These findings identify Sap10 as a fungal ligand of DNAM-1 and reveal a mechanism by which NK cells recognize fungal pathogens.