Bovine NK cells acquire cytotoxic activity and produce IFN-γ after stimulation by Mycobacterium bovis BCG- or Babesia bovis-exposed splenic dendritic cells

• Published in: Veterinary immunology and immunopathology Vol. 124; no. 3; pp. 302 - 312
• Main Authors: Bastos, R.G., Johnson, W.C., Mwangi, W., Brown, W.C., Goff, W.L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15-08-2008; Amsterdam: Elsevier
• Subjects: Animals; B7-1 Antigen - immunology; B7-2 Antigen - immunology; Babesia bovis; Babesia bovis - immunology; Babesiosis; biochemical mechanisms; Bovine; Cattle; cell culture; cell physiology; Coculture Techniques; Cytotoxicity; Cytotoxicity, Immunologic; dendritic cells; Dendritic Cells - immunology; Dendritic Cells - microbiology; disease resistance; Flow Cytometry - veterinary; gamma-interferon; Granulocyte-Macrophage Colony-Stimulating Factor - immunology; Histocompatibility Antigens Class II - immunology; IFN-gamma; immune response; immune system; immunity; in vitro studies; Innate immunity; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; interferons; Interleukin-4 - immunology; Killer Cells, Natural - immunology; Killer Cells, Natural - microbiology; lymphocytes; Male; Membrane Proteins - immunology; Mycobacterium bovis - immunology; Mycobacterium bovis BCG; natural killer cells; NK cells; phenotype; spleen; Splenic dendritic cells; T-lymphocytes; Splenic dendritic cells; NK cells; Bovine; IFN-gamma; Babesiosis; Innate immunity; Cytotoxicity
• ISSN: 0165-2427; 1873-2534
• DOI: 10.1016/j.vetimm.2008.04.004

Early interactions of innate immune cell populations, such as dendritic cells (DC) and natural killer (NK) cells, can affect the ability of the acquired immune response to control infection of intracellular microorganisms. In this study, we investigated the activation of bovine NK cells by CD13
+ splenic DC stimulated with either
Mycobacterium bovis BCG or
Babesia bovis merozoites. Splenic DC were used either immediately after selection (cytokine
−) or after exposure to GM-CSF, IL-4 and Flt3L for 72
h (cytokine
+). Phenotypic analyses showed up-regulation of MHCII, CD80 and CD86 on cytokine
+ DC when compared to cytokine
− DC. Purified NK cells (CD335
+CD3
−CD2
+/−CD8α
+/−) were co-cultured with microbial-exposed cytokine
− DC or cytokine
+ DC in either transwell or cell-to-cell format and NK cell IFN-γ production and cytotoxicity were assessed. NK cell IFN-γ production was dependent on cell-to-cell contact. Microbial-stimulated cytokine
+ DC induced significantly more IFN-γ production from NK cells than cytokine
− cells. In contrast, cytotoxicity and perforin up-regulation were more pronounced in NK cells cultured with cytokine
− DC than cytokine
+ DC. Therefore, activation of bovine NK cells by microbial-stimulated CD13
+ splenic DC is influenced by the maturation state of the DC suggesting different roles for the splenic DC during disease-induced maturation.