Distinct Gut-Derived Bacteria Differentially Affect Three Types of Antigen-Presenting Cells and Impact on NK- and T-Cell Responses

Objectives Gut bacteria are assumed essential for development and maintenance of a balanced immune system. Specifically, stimulation of antigen-presenting cells (APCs) by gut bacteria is important for polarisation of the immune response. This experiment was designed to reveal similarities and differences between the reaction patterns of three types of human APCs when stimulated with intestinal bacteria. Furthermore, the effect of these APCs on NK-cells and T-cells was examined. Methodology The APCs used in this study were blood monocytes, blood dendritic cells, and dendritic cells differentiated from monocytes. Monocyte-derived dendritic cells constitute a commonly used model of dendritic cell function. The APCs were cultured for 18 h with four different gut bacteria: Lactobacillus acidophilus X37, Lactobacillus reuteri DSM 12246, E. coli Nissle 1917 or Bifidobacterium longum Q46. Results & Discussion To examine the polarising effect of gut bacteria on APCs, surface markers and cytokines were measured. The co-stimulatory molecules CD40 and CD86 were induced to a different extent together with CD83. Interleukin-12 (a Th1 cytokine) was only induced by Lactobacillus acidophilus. Interleukin-10, which promotes the development of regulatory T-cells, was mainly induced by the other bacteria. Interleukin-6 and tumour necrosis factor are pro-inflammatory cytokines, often induced by pathogens, but also by some gut bacteria. The effect of the four gut bacteria on monocyte-derived dendritic cells has previously been examined, but this study revealed that their effect on other kinds of APCs is markedly different. When APCs matured by different bacteria were added to either NK-cells or T-cells, different APCs combined with distinct strains of bacteria caused the production of varying amounts of cytokines. Conclusions Distinct gut bacteria possess individual properties leading to different effects on APCs, NK-cells and T-cells. Because NK-cells play a major role in T-cell polarisation, and because the APCs affect T-cells directly, gut bacteria may be very important in maintaining a balanced immune response through these mechanisms. The bacteria examined can potentially be used in tailored probiotic foods exploring their immunomodulatory properties.