The recent characterisation of bovine NK cells and the availability of a monoclonal antibody against the NKp46 receptor have facilitated a study of the role of these cells in bovine mycobacterial infections. NK cells are important in initiating Th1 immune responses necessary for protection against bovine tuberculosis and paratuberculosis. The present study focused on the interaction between NK cells, antigen presenting cells and secreted mycobacterial proteins. IFN-γ production by NK cells was seen in non-infected calves in response to the Mycobacterium tuberculosis complex specific protein ESAT-6, MPP14 from Mycobacterium avium subspecies paratuberculosis, and PPD from M. tuberculosis. In contrast, no response was induced by MPB70. The production of IFN-γ by NK cells in whole blood was demonstrated using intracellular staining together with surface labelling for NKp46 or CD3. Furthermore, the depletion of NK cells from peripheral blood mononuclear cells completely abolished the IFN-γ production. The response was mediated through stimulation of adherent cells and was largely independent of contact between adherent cells and the NK cells. Neutralisation of IL-12 only partly inhibited IFN-γ production showing that other cytokines also were involved. The demonstration of IFN-γ production from NK cells have implication for the IFN-γ test used for diagnosis of mycobacterial infections. It is well recognised that the test cannot be used in young cattle due to a large proportion of non-specific reactors. It has been proposed that this is due to sensitisation to other mycobacteria, but our results suggest that NK cells are the source for IFN-γ in these animals. There has been a lot of focus on identification of specific antigens to improve the specificity of the IFN-γ test, but our results indicate that further research also should focus on methods that inhibit IFN-γ production from NK cells.

Sponsorship

Attendance to this Congress was sponsored by the EU-funded project SSPE-CT-2004-501903