Human NK cells directly recognize Mycobacterium bovis via TLR2 and acquire the ability to kill monocyte-derived DC

Emanuela Marcenaro, Bruna Ferranti, Michela Falco, Lorenzo Moretta, Alessandro Moretta

Research output: Contribution to journalArticlepeer-review

Abstract

NK cells are important players of the early innate defense against various pathogens. In this study, we investigated the interaction between human NK cells and Mycobacterium bovis [bacille Calmette-Guérin (BCG)] and we determined whether and how such an interaction might impact on NK cell activation, cytokine production and cytotoxicity. We show that highly purified NK cells, upon short-term co-culture with BCG, expressed activation markers including CD69 and CD25. Moreover, these NK cells released IFN-gamma and tumor necrosis factor-alpha and killed more efficiently different targets including monocyte-derived immature dendritic cell. All these functions were strongly up-regulated in the presence of exogenous IL-12. Although more efficient responses were detected in NK cell populations displaying an NCRbright phenotype, no direct evidence of an involvement of triggering NK receptors in BCG recognition could be obtained. On the other hand, anti-toll-like receptor (TLR)2 mAb inhibited NK cell responses to BCG, suggesting that NK cells may express a functional TLR2, which plays a role in their mechanism of direct BCG recognition. Taken together, these data suggest that BCG, by inducing simultaneous activation of NK and antigen-presenting cells via their 'shared' TLR2, can promote efficient bidirectional NK-dendritic cell interactions necessary for subsequent priming of Th1 responses.

Original languageEnglish
Pages (from-to)1155-1167
Number of pages13
JournalInternational Immunology
Volume20
Issue number9
DOIs
Publication statusPublished - 2008

Keywords

  • Cytokine release
  • Cytotoxicity
  • Mycobacterium bovis bacille Calmette-Guérin
  • NK cells
  • Toll-like receptors

ASJC Scopus subject areas

  • Immunology

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