Human Dendritic Cell DC-SIGN and TLR-2 Mediate Complementary Immune Regulatory Activities in Response to Lactobacillus rhamnosus JB-1

Abstract

The microbiota is required for optimal host development and ongoing immune homeostasis. Lactobacilli are common inhabitants of the mammalian large intestine and immunoregulatory effects have been described for certain, but not all, strains. The mechanisms underpinning these protective effects are beginning to be elucidated. One such protective organism is Lactobacillus rhamnosus JB-1 (Lb. rhamnosus JB-1). Lb. murinus has no such anti-inflammatory protective effects and was used as a comparator organism. Human monocyte-derived dendritic cells (MDDCs) were co-incubated with bacteria and analysed over time for bacterial adhesion and intracellular processing, costimulatory molecule expression, cytokine secretion and induction of lymphocyte polarization. Neutralising antibodies were utilized to identify the responsible MDDC receptors. Lb. rhamnosus JB-1 adhered to MDDCs, but internalization and intracellular processing was significantly delayed, compared to Lb. murinus which was rapidly internalized and processed. Lb. murinus induced CD80 and CD86 expression, accompanied by high levels of cytokine secretion, while Lb. rhamnosus JB-1 was a poor inducer of costimulatory molecule expression and cytokine secretion. Lb. rhamnosus JB-1 primed MDDCs induced Foxp3 expression in autologous lymphocytes, while Lb. murinus primed MDDCs induced Foxp3, T-bet and Ror-γt expression. DC-SIGN was required for Lb. rhamnosus JB-1 adhesion and influenced IL-12 secretion, while TLR-2 influenced IL-10 and IL-12 secretion. Here we demonstrate that the delayed kinetics of bacterial processing by MDDCs correlates with MDDC activation and stimulation of lymphocytes. Thus, inhibition or delay of intracellular processing may be a novel strategy by which certain commensals may avoid the induction of proinflammatory responses.

The probiotic activity of Lactobacillus murinus against food allergy

“…The suppressed OX40L expression is in parallel with the Th1-promoting properties of L. murinus, and indicates that DC functions are modulated.This notion is substantiated by our results showing that the level of IL-12 mRNA and the number of CD11c + cells expressing IL-12 were increased in the intestine of allergic mice treated with L. murinus. The enhanced IL-12 expression by L. murinus is consistent with previous results observed in human monocytederived DC (Konieczna et al, 2015). Taken together, these lines of evidence indicate that L. murinus may enhance Th1 cellmediated immunity by up-regulating DC functionality.…”

Role of Regulatory Cells in Oral Tolerance

“…Furthermore, certain bacterial strains, such as Bifidobacterium longum 35624, Clostridia and Bacterioides fragilis can induce intestinal Treg cells that are capable of suppressing food allergy and colitis 6061. Pattern-recognition receptor activation on DC seems to be an important mechanism by which intestinal microbes may promote Treg cell differentiation 62. On the other hand, intestinal microbes, such as segmented filamentous bacteria, can also promote the development of Th17 rather than Treg cells.…”

Genome-Wide Immune Modulation of TLR3-Mediated Inflammation in Intestinal Epithelial Cells Differs between Single and Multi-Strain Probiotic Combination

“…Studies of immune-modulation of TLR-mediated responses have mainly focused on the effects of different strains of Lactobacillus rhamnosus and include the differential expression of TLR genes in human primary macrophages [17], polarization of human monocyte-derived dendritic cells via TLR2 [18] and the attenuation of TLR4-induced signaling in Escherichia coli- challenged immune cells [19,20]. L .…”