Investigating immunomodulating mechanisms of probiotics

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Probiotics are 'living micro-organisms that when administered in adequate amounts confer a health benefit to the host'. An increasing number of studies provide scientific evidence for the efficacy and efficiency of probiotics in alleviating several inflammatory diseases. However, the specific mechanisms by which probiotic bacteria contribute to health, and, especially, their anti-inflammatory properties remain poorly understood. This research program is to investigate the signaling and molecular immunomodulatory mechanisms of probiotics. We have shown that probiotic strains of Lactobacillus rhamnosus are potent inducers of G-CSF production, which suppresses production of the pro-inflammatory cytokine tumor necrosis factor (TNF) in activated macrophages. We hypothesize that L. rhamnosus preferentially induces G-CSF in monocytes/macrophages, which is a key anti-inflammatory cytokine mediating immunomodulatory effects on macrophages and dendritic cells. To address the hypothesis, we propose the following four specific research objectives: 1) Investigating the signaling mechanism of G-CSF production in L. rhamnosus-activated macrophages, 2) Investigating the effect of G-CSF on macrophages, 3) Investigating the mechanism of G-CSF in regulating macrophage activation and 4) Investigating the role of G-CSF on dendritic cells.