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* Division of Immunology, Department of Pathology, University of Cambridge, Cambridge, U.K.; and
Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Institut National de la Santé et de la Recherche Médicale, Unité 631, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6102, Marseille, France
NK cells play a key role in host resistance to a range of pathogenic microorganisms, particularly during the initial stages of infection. NK cell interactions with cells infected with viruses and parasites have been studied extensively, but human bacterial infections have not been given the same attention. We studied crosstalk between human NK cells and macrophages infected with intracellular Salmonella. These macrophages activated NK cells, resulting in secretion of IFN-
and degranulation. Reciprocally, NK cell activation led to a dramatic reduction in numbers of intramacrophagic live bacteria. We identified three elements in the interaction of NK cells with infected macrophages. First, communication between NK cells and infected macrophages was contact-dependent. The second requirement was IL-2- and/or IL-15-dependent priming of NK cells to produce IFN-. The third was activation of NK cells by IL-12 and IL-18, which were secreted by the Salmonella-infected macrophages. Adhesion molecules and IL-12Rβ2 were enriched in the contact zone between NK cells and macrophages, consistent with contact- and IL-12/IL-18-dependent NK activation. Our results suggest that, in humans, bacterial clearance is consistent with a model invoking a "ménage à trois" involving NK cells, IL-2/IL-15-secreting cells, and infected macrophages.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 E.V.’s laboratory is supported by the European Union ("Allostem"), Ligue National contre le Cancer ("Equipe Labellisée"), Agence National de la Recherche, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Ministère de l’Enseignement Supérieur et de la Recherche and Institut Universitaire de France. S.M. was supported by a grant from the Fondation pour la Recherche Médicale ("Equipe FRM"). J.T.’s laboratory is supported by the Wellcome Trust and the Medical Research Council. N.L. was supported by a Marie-Curie Research Training Network, Microban European Union Network (RTN-CT-2003-504227), with partial funding from the National Institute for Health Research Cambridge Biomedical Research Centre.
2 Address correspondence and reprint requests to Dr. Nicolas Lapaque, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, U.K. E-mail address: nl255{at}cam.ac.uk
3 The online version of this article contains supplemental material.
This article has been cited by other articles:
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  E. A. Haddad, L. K. Senger, and F. Takei An Accessory Role for B Cells in the IL-12-Induced Activation of Resting Mouse NK Cells J. Immunol., September 15, 2009; 183(6): 3608 - 3615. [Abstract] [Full Text] [PDF]
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