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<p>Natural Killer (NK) cells can recognize and kill <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>)-infected cells in vitro, however their role after natural human exposure has not been well-studied. To identify <i>Mtb</i>-responsive NK cell populations, we analyzed the peripheral blood of healthy household contacts of active Tuberculosis (TB) cases and source community donors in an endemic region of Port-au-Prince, Haiti by flow cytometry. We observed higher CD8α expression on NK cells in putative resistors (Interferon&#xa0;γ release assay negative;&#xa0;IGRA− contacts) with a loss of CD8α surface expression during household-associated exposure and active TB disease. In vitro assays and CITE-seq analysis of CD8α<sup>+</sup> NK cells demonstrated enhanced maturity, cytotoxic gene expression, and response to cytokine stimulation relative to CD8α<sup>−</sup> NK cells. CD8α<sup>+</sup> NK cells also displayed dynamic surface expression dependent on MHC class I in contrast to conventional CD8<sup>+</sup> T cells. Together, these results support a specialized role for CD8α<sup>+</sup> NK cell populations during <i>Mtb</i> infection correlating with disease resistance.</p>

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CD8α marks a Mycobacterium tuberculosis-reactive human NK cell population with high activation potential

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月29日

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  • Nezar Mehanna,
  • Atul Pradhan,
  • Rimanpreet Kaur,
  • Theodota Kontopoulos,
  • Barbara Rosati,
  • David Carlson,
  • Nai-Kong V. Cheung,
  • Hong Xu,
  • James Bean,
  • Katharine C. Hsu,
  • Jean-Benoit Le Luduec,
  • Charles Kyriakos Vorkas

摘要

Natural Killer (NK) cells can recognize and kill Mycobacterium tuberculosis (Mtb)-infected cells in vitro, however their role after natural human exposure has not been well-studied. To identify Mtb-responsive NK cell populations, we analyzed the peripheral blood of healthy household contacts of active Tuberculosis (TB) cases and source community donors in an endemic region of Port-au-Prince, Haiti by flow cytometry. We observed higher CD8α expression on NK cells in putative resistors (Interferon γ release assay negative; IGRA− contacts) with a loss of CD8α surface expression during household-associated exposure and active TB disease. In vitro assays and CITE-seq analysis of CD8α+ NK cells demonstrated enhanced maturity, cytotoxic gene expression, and response to cytokine stimulation relative to CD8α− NK cells. CD8α+ NK cells also displayed dynamic surface expression dependent on MHC class I in contrast to conventional CD8+ T cells. Together, these results support a specialized role for CD8α+ NK cell populations during Mtb infection correlating with disease resistance.