Memory like NK cells display stem cell like properties after Zika virus infection

PLoS Pathog. 2020 Dec 28;16(12):e1009132. doi: 10.1371/journal.ppat.1009132. eCollection 2020 Dec.

Abstract

NK cells have been shown to display adaptive traits such as memory formation akin to T and B lymphocytes. Here we show that Zika virus infection induces memory like NK cells that express CD27. Strikingly, these cells exhibit stem-like features that include expansion capacity, self-renewal pathway, differentiation into effector cells, longer telomeres and gene signature associated with hematopoietic stem cell (HSC) progenitors. This subset shared transcriptional and epigenetic changes with memory CD8 T cells, stem cells and stem like T cells. These NK cells with memory and stem cell features, which we term "NK memory stem cells", demonstrated greater antiviral potential than CD27- or naïve CD27+ NK when adoptively transferred to Zika infected mice. Our results also suggest a role for the transcription factor TCF-1 in memory and stemness features of this NK subset. This study defines a unique TCF1hi CD27+ NK subset with memory capacity and stem cell features that play a role in antiviral immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Immunologic Memory / immunology*
  • Killer Cells, Natural / immunology*
  • Lymphocyte Subsets / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Stem Cells / immunology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology
  • Zika Virus Infection / immunology*

Substances

  • Tumor Necrosis Factor Receptor Superfamily, Member 7

Grants and funding

This work was supported by University of Texas STARS award to S.M. and Department of Pulmonary Immunology, University of Texas Health Science Center at Tyler, Texas, USA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.