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.
Highlights
It is well accepted that the gut microbiota plays a pivotal role in mucosal immune system development and ongoing homeostasis [1,2,3]
In order to further investigate the receptors that may be involved in monocyte-derived dendritic cells (MDDCs) recognition of Lb. rhamnosus JB-1, we examined the role for dendritic cells (DCs)-SIGN and TLR-2 as they have been doi:10.1371/journal.pone.0120261.g002
In this report we demonstrate that the kinetics of DC processing and the magnitude of cellular activation induced by Lb. rhamnosus JB-1 are significantly different than that of another strain, Lb. murinus
Summary
It is well accepted that the gut microbiota plays a pivotal role in mucosal immune system development and ongoing homeostasis [1,2,3]. A diverse gut microbiota contributes to appropriate digestion of dietary substances, protects against pathobiont expansion, provides nutrients for the host and ensures appropriate development of the mucosal barrier [4,5,6]. The mechanisms underpinning these protective responses are varied and include intact microbial cell interaction with host receptors, and microbial metabolic activity, including short chain fatty acid production and bile degradation, which influences biological functions of the whole organism [7,8,9]. Not all Lactobacillus strains exert the same effects, for example Lactobacillus salivarius AH102 does not induce T regulatory cells [18]
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