Background: The resident host microflora condition and prime the immune system. However, systemic and mucosal immune responses to bacteria may be divergent. Aim: To compare, in vitro, cytokine production by human mononuclear and dendritic cells from mesenteric lymph nodes (MLN) and peripheral blood mononuclear cells (PBMCs) to defined microbial stimuli. Methods: Mononuclear cells and dendritic cells, isolated from MLN (n=10) and peripheral blood (n=12) of patients with active colitis, were incubated in vitro with the probiotic bacteria, Lactobacillus salivarius UCC118 or Bifidobacterium infantis 35624, or the pathogenic organism Salmonella typhimurium UK1. IL-12, TNF-, TGF- and IL-10 cytokine levels were quantified by ELISA. Results: PBMCs and PBMC-derived DCs secreted TNF- in response to the lactobacillus, bifidobacteria and salmonella strains, while MLNCs and MLN derived DCs secreted TNF- only in response to salmonella challenge. Cells from the systemic compartment secreted IL-12 following co-incubation with salmonella or lactobacilli, while MLN derived cells produced IL-12 only in response to salmonella. PBMCs secreted IL-10 in response to the bifidobacterium strain, but not in response to the lactobacillus or salmonella strain. However, MLNC secreted IL-10 in response to bifidobacteria and lactobacilli, but not in response to salmonella. Conclusion: Commensal bacteria induced regulatory cytokine production by MLNCs while pathogenic bacteria induce Th1 polarising cytokines. Commensal-pathogen divergence in cytokine responses are more marked in cells isolated from the mucosal immune system compared to peripheral blood mononuclear cells.