Lactobacilli Modulate Proliferation and Cytokine Production of Human Peripheral Blood Natural Killer Cells In Vitro

Fink, L. N.; Christensen, H. R.; Frøkiær, H.

Natural killer (NK) cells are cells of the nonspecific immune system lysing altered self‐cells. A noncytolytic subset of NK cells may serve a regulatory role by secreting cytokines. Bacteria translocating across the gastrointestinal mucosa are presumed to gain access to NK cells, as consumption of certain lactic acid bacteria has been shown to increase in vivo NK cytotoxicity. Here, we investigated how human gut flora‐derived lactobacilli affect NK cells in vitro, by measuring proliferation and IFN‐γ production of human NK cells upon bacterial stimulation. CD3(–)CD56(+)NK cells were isolated from buffy coats by negative isolation using non‐NK lineage‐specific antibodies and magnetic beads. NK cells were incubated with 10μg/ml UV‐inactivated bacteria or 10μg/ml phytohemagglutinin (PHA) for 4 days. Proliferation was assessed by incorporation of radioactive thymidine into NK‐cell DNA. The IFN‐γ concentration was measured by ELISA. Incubation of NK cells with a Lactobacillus acidophilus strain increased the proliferation of the NK cells and induced IFN‐γ production, both to levels comparable to PHA stimulation. The proliferative response was further enhanced with autologous monocytes present, probably because cytokines, secreted by monocytes having engulfed bacteria, stimulated the NK cells. In contrast, a Lactobacillus paracasei strain caused the NK cells to proliferate only in the presence of monocytes. These results demonstrate that various strains of lactobacilli have the capacity to activate NK cells in vitro, in a monocyte‐dependent or ‐independent way. Hence, the encounter of NK cells with lactic acid bacteria will affect NK‐cell activation. Such activation of NK cells may potentially skew an on‐going or subsequent immune response towards a Th1 response.