Background: Natural killer (NK) cells are lymphocytes of the non-specific immune system recognizing cancerous cells and cells altered by viral infection. Recently, it was proposed that a non-cytolytic subset of NK cells serves a regulatory role by secreting cytokines, possibly affecting both antigen presenting cells and T-cells. Bacteria translocating across the gastrointestinal mucosa are presumed to gain access to NK cell compartments, as consumption of certain strains of lactic acid bacteria has been shown to increase in vivo NK cytotoxic activity. On-going research in our lab aims at describing strain-dependent effects of lactic acid bacteria on regulatory functions of NK-cells. Here, we have investigated how human gut flora-derived non-pathogenic lactic acid bacteria affect NK cells in vitro, by measuring proliferation and IFN-gamma production of human peripheral blood NK cells upon bacterial stimulation. Methods: CD3-CD56+ NK cells were isolated from buffy coats by negative isolation using a lineage specific antibody cocktail and magnetic beads binding the labelling antibodies on non-NK cells. NK cells were incubated either with 10 microg/ml UV-inactivated lactic acid bacteria or 10 microg/ml phytohemagglutinin (PHA) as a proliferation control. Proliferation was assessed by incorporation of radioactive thymidine into NK cell DNA. Cytokine concentrations were determined by ELISA. Results: Co-incubation of NK cells and a Lactobacillus acidophilus strain for four days caused increased proliferation of the NK cells and induced IFN-gamma production, both to levels comparable to PHA stimulation. The proliferative response was further enhanced when autologous monocytes were present, probably because cytokines secreted by monocytes having engulfed bacteria stimulated the growth of the NK cells. In contrast, a Lactobacillus paracasei strain caused the NK cells to proliferate only in the presence of monocytes. Conclusion: In this study we have demonstrated that various strains of gut flora-derived lactic acid bacteria have the capacity to activate NK cells in vitro, in a monocyte dependent or independent way. Our results indicate that if NK cells encounter lactic acid bacteria or components hereof in the gut mucosa, this affects NK cell activation by inducing proliferation and cytokine production. Such activation of NK cells may potentially skew an on-going or subsequent immune response towards a Th1 response.
|Publication status||Published - 2004|
|Event||12th International Congress of Immunology - Montreal, Canada|
Duration: 1 Jan 2004 → …
|Conference||12th International Congress of Immunology|
|Period||01/01/2004 → …|