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 translocation through the epithelial barrier cannot be excluded. In this study the stimulation of human peripheral blood mononuclear cells and purified lymphocyte subsets by nonpathogenic gram-positive lactobacilli (Lactobacillus johnsonii and Lactobacillus sakei) and gram-negative Escherichia coli was investigated. The various bacterial strains induced a differential cytokine pattern. Whereas L. johnsonii and L. sakei strongly induced gamma interferon (IFN-γ) and interleukin-12 (IL-12), E. coli and lipopolysaccharide (LPS) preferentially induced IL-10 after 16 h of stimulation. Expression of activation antigens CD69 and CD25 was observed on (CD3^- CD56⁺) natural killer (NK) cells after stimulation of total human peripheral blood mononuclear cells. All bacteria mediated the proliferation of human peripheral blood mononuclear cells, and the strongest proliferative response was observed with L. johnsonii. Purified CD4⁺, CD8⁺, and CD19⁺ lymphocyte subsets were not activated upon bacterial stimulation but showed normal response to a mitogenic stimulus. In contrast, purified NK cells upregulated the IL-2Rα chain (CD25) and underwent proliferation when stimulated by L. johnsonii. E. coli and LPS were less effective in inducing proliferation. Expression of CD25 or secretion of IFN-γ from purified NK cells was significantly increased in the presence of bacterially primed macrophages, indicating that full activation required both bacterium- and cell contact-based signals derived from accessory cells.