International Immunology Advance Access originally published online on July 1, 2008
International Immunology 2008 20(9):1155-1167; doi:10.1093/intimm/dxn073
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Human NK cells directly recognize Mycobacterium bovis via TLR2 and acquire the ability to kill monocyte-derived DC
1 Dipartimento di Medicina Sperimentale, Università di Genova, Genova, Italy
2 Istituto Giannina Gaslini, Genova, Italy
3 Centro di Eccellenza per la Ricerca Biomedica, Genova, Italy
Correspondence to: A. Moretta; E-mail: alemoret{at}unige.it
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.
Keywords: cytokine release, cytotoxicity, Mycobacterium bovis bacille Calmette–Guérin, NK cells, toll-like receptors
Transmitting editor: E. Vivier
Received 1 April 2008, accepted 5 June 2008.
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