Activation of human peripheral blood mononuclear cells by nonpathogenic bacteria in vitro: Evidence of NK cells as primary targets

The interaction of commensal bacteria with immunocompetent cells may occur in definite compartments of the mucosal immune system, as limited transloca tion through the epithelial barrier cannot be excluded. In this study the s timulation of human peripheral blood mononuclear cells and purified lymphoc yte subsets by nonpathogenic gram-positive lactobacilli (Lactobacillus john sonii and Lactobacillus sakei) and gram-negative Escherichia coli was inves tigated, The various bacterial strains induced a differential cytokine patt ern. Whereas L.. johnsonii and L. sakei strongly induced gamma interferon ( IFN-gamma) and interleukin-12 (IL-12), E. coli and lipopolysaccharide (LPS) preferentially induced IL-10 after 16 h of stimulation. Expression of acti vation antigens CD69 and CD25 was observed on (CD3(-) CD56(+)) natural kill er (NK) cells after stimulation of total human peripheral blood mononuclear cells. All bacteria mediated the proliferation of human peripheral blood m ononuclear cells, and the strongest proliferative response was observed wit h L. johnsonii. Purified CD4(+), CD8(+), and CD19(+) lymphocyte subsets wer e not activated upon bacterial stimulation but showed normal response to a mitogenic stimulus. In contrast, purified NK cells upregulated the IL-2R al pha chain (CD25) and underwent proliferation when stimulated by L, johnsoni i, E, coli and LPS were less effective in inducing proliferation. Expressio n of CD25 or secretion of IFN-gamma from purified NK cells was significantl y increased in the presence of bacterially primed macrophages, indicating t hat full activation required both bacterium- and cell contact-based signals derived from accessory cells.