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Infection and Immunity, September 2005, p. 5628-5635, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5628-5635.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Bovine NK Cells Can Produce Gamma Interferon in Response to the Secreted Mycobacterial Proteins ESAT-6 and MPP14 but Not in Response to MPB70

Ingrid Olsen,1* Preben Boysen,2 Siri Kulberg,1,2 Jayne C. Hope,3 Gregers Jungersen,4 and Anne K. Storset2

National Veterinary Institute, Oslo,1 Norwegian School of Veterinary Science, Oslo, Norway,2 Institute for Animal Health, Compton, United Kingdom,3 Danish Institute for Food and Veterinary Research, Copenhagen, Denmark4

Received 7 March 2005/ Returned for modification 12 April 2005/ Accepted 20 April 2005

Bovine NK cells have recently been characterized and the present study describes the interaction between NK cells, antigen-presenting cells, and secreted mycobacterial proteins. Gamma interferon (IFN-{gamma}) production by NK cells was seen in approximately 30% of noninfected calves in response to the Mycobacterium tuberculosis complex-specific protein ESAT-6, MPP14 from Mycobacterium avium subsp. paratuberculosis, and purified protein derivative (PPD) from M. tuberculosis. In contrast, no response was induced by MPB70, which is another M. tuberculosis complex-specific secreted antigen. The production of IFN-{gamma} by NK cells in whole blood in response to ESAT-6 and MPP14 was demonstrated using intracellular staining together with surface labeling for the NK cell-specific receptor, NKp46, or CD3. Furthermore, the depletion of NK cells from peripheral blood mononuclear cells completely abolished the IFN-{gamma} production. The response was mediated through stimulation of adherent cells and was largely independent of contact between adherent cells and the NK cells. Neutralization of interleukin-12 only partly inhibited IFN-{gamma} production, showing that other cytokines were also involved. The demonstration of NK cell-mediated IFN-{gamma} production in young cattle provides an explanation for the nonspecific IFN-{gamma} response frequently encountered in young cattle when using the IFN-{gamma} test in diagnosis of mycobacterial infections.

* Corresponding author. Mailing address: National Veterinary Institute, P.O. Box 8156 Dep., 0033 Oslo, Norway. Phone: 47 23 21 63 32. Fax: 47 23 21 63 02. E-mail: Ingrid.Olsen{at}vetinst.no.

Editor: J. D. Clements

Infection and Immunity, September 2005, p. 5628-5635, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5628-5635.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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