Receptor modulation and functional activation of human CD34+Lin--derived immature NK cells in vitro by Mycobacterium bovis Bacillus Calmette-Guerin (BCG)

Francesco Marras, Federica Bozzano, Giorgio Bentivoglio, Elisabetta Ugolotti, Roberto Biassoni, Lorenzo Moretta, Andrea De Maria

Research output: Contribution to journalArticlepeer-review

Abstract

It is not yet clear whether immature NK (iNK) cells are bystanders to or rather participate in immune responses to pathogens that may colocalize in areas of NK-cell maturation such as bone marrow or lymph nodes. Mycobacteria, including Bacillus Calmette-Guerin (BCG), have been shown to interact with peripheral NK cells and in vivo may colocalize in areas of iNK-cell development. We studied infection with BCG of human cord blood CD34+Lin--derived cultures containing myelomonocytes and iNK cells in vitro. Increased iNK-cell DNAM-1 expression, transient natural cytotoxicity receptor modulation, and production of IFN-γ were observed. Transcriptional receptor modulation was associated to BCG challenge, which determined increased iNK-cell cytotoxic activity against tumor cell lines and also increased killing of immature dendritic cells (iDCs). No requirement for cell contact was recorded for BCG-induced iNK-cell activation, while cytokine production including IL-18, IL-10, GM-CSF, and TGF-β contributed to the observed effects. Thus, iNK cells are affected by mycobacteria in vitro and may contribute to shaping of adaptive mature innate responses through iDC-iNK cross-talk. In addition, iNK-cell activation by BCG may represent a novel additional mechanism contributing to the effects observed upon BCG administration in vivo.

Original languageEnglish
Pages (from-to)2459-2470
Number of pages12
JournalEuropean Journal of Immunology
Volume42
Issue number9
DOIs
Publication statusPublished - Sep 2012

Keywords

  • BCG
  • DNAM-1
  • Maturing NK cell
  • Mycobacteria
  • Natural cytotoxicity receptors

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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