Cytokine secretion by stimulated monocytes depends on the growth phase and heat treatment of bacteria: a comparative study between lactic acid bacteria and invasive pathogens.

The consumption of food containing lactic acid bacteria (LAB) has been shown to exert immunomodulatory effects in humans. The specific cellular interaction of these bacteria with immuno-competent cells has not yet been fully understood. Since the TNF-alpha secretion of stimulated monocytes is an important initial response to a bacterial challenge, we investigated the potential of LAB originating from the human intestine or fermented food in comparison to the effect of invasive pathogens. The challenge of monocytes with three LAB strains, Listeria monocytogenes or enterohaemorrhagic Escherichia coli (EHEC) elicited a strain specific, dose-dependent biphasic TNF-alpha secretion. The concentration (EDmax) of bacteria or bacterial cell wall components necessary to induce maximal TNF-alpha secretion (TNFmax) by monocytes was mathematically approximated. It was shown for exponentially growing LAB strains that the maximal TNF-alpha secretion (TNFmax) was stronger (57 to 78%) upon stimulation with living bacteria than with heat killed cells. In contrast to log-phase bacteria, the maximal TNF-alpha secretion of monocytes (TNFmax) was higher (15 to 55%) after the stimulation with heat killed, stationary-phase bacteria when compared to that of live LAB. Thus, monocyte stimulation was clearly affected by the growth phase of bacteria. Purified cell walls of LAB strains revealed only a limited potential for monocyte stimulation. LPS exhibited a higher capacity to stimulate monocytes than purified gram positive cell walls or muramyldipeptide. In comparison to pathogenic bacteria, the maximal secretory TNF-alpha response (TNFmax) was up to 2 fold higher with LAB strains. In general, the amount of bacteria (EDmax) necessary to induce maximal TNF-alpha secretion (TNFmax) was approximately 1 to 3 log higher for heat killed bacteria when compared to live bacterial cells illustrating the significant lower potential of heat killed bacteria to activate monocytes.