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International Immunology Advance Access originally published online on October 20, 2007
International Immunology 2007 19(12):1319-1327; doi:10.1093/intimm/dxm103
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© The Japanese Society for Immunology. 2007. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Distinct gut-derived lactic acid bacteria elicit divergent dendritic cell-mediated NK cell responses

Lisbeth N. Fink1, Louise H. Zeuthen1, Hanne R. Christensen1,4, Barbara Morandi2,3, Hanne Frøkiær1,* and Guido Ferlazzo2,3,*

1 Center for Biological Sequence Analysis, BioCentrum-DTU, Technical University of Denmark, Kongens Lyngby, Denmark
2 Laboratory of Immunology, Istituto Nazionale per la Ricerca sul Cancro (IST), Genoa, Italy
3 Laboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina, Messina, Italy
4 Present address: Novo Nordisk A/S, DK-2880, Bagsværd, Denmark

Correspondence to: L. N. Fink; E-mail: lnf{at}biocentrum.dtu.dk

Lactic acid bacteria (LAB) are abundant in the gastrointestinal tract where they continuously regulate the immune system. NK cells are potently activated by dendritic cells (DCs) matured by inflammatory stimuli, and NK cells are present in the gut epithelium and in mesenteric lymph nodes, but it is not known how NK–DC interactions are affected by the predominantly non-pathogenic LAB. We demonstrate that human DCs exposed to different strains of gut-derived LAB consistently induce proliferation, cytotoxicity and activation markers in autologous NK cells. On the contrary, strains of LAB differ greatly in their ability to induce DC-dependent IFN-{gamma} production by NK cells. This suggests that DCs stimulated by gut LAB may expand the pool of NK cells and increase their cytotoxic potential. Specific LAB, inducing high levels of IL-12 in DCs, may promote amplification of a type-1 response via potent stimulation of IFN-{gamma} production in NK cells. Combining IFN-{gamma}-inducing and non-inducing LAB completely abrogates DC-mediated IFN-{gamma} production by NK cells, and therefore LAB modulating IFN-{gamma} production in NK cells may be important regulators of the immune response.

Keywords: cytokines, cytotoxicity, intestinal bacteria, probiotics

* These authors contributed equally to this study.

Transmitting editor: L. Moretta

Received 22 April 2007, accepted 20 September 2007.


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