title: Modulation of Toll-like receptor ligands and Candida albicans-induced cytokine responses by specific probiotics.
abstract: Probiotics have been proposed as modulators of gut inflammation, especially in inflammatory bowel disease (IBD). In order to be able to use them in these clinical conditions, their capacity to modulate immune responses towards other stimuli or microorganisms has to be thoroughly understood. In the present study, three different potentially probiotic strains, Bifidobacterium breve (NumRes 204), Lactobacillus rhamnosus (NumRes1) and Lactobacillus casei (DN-114 001), have been studied for their potential to modulate responses to stimulation with pure pattern-recognition receptor (PRR) ligands or to the gut commensal fungus Candida albicans. Cytokine production induced by PRR ligands or C. albicans was assessed in conditions of simultaneous stimulation or preincubation of primary immune cells with Bifidobacterium or Lactobacillus spp. Results indicate that simultaneous stimulation leads to potentiation of IL-1β and IL-6 production, while the TNFα and IFN-γ production was inhibited. In settings of pre-incubation with these potentially probiotic strains, lower production of TNFα was observed in the presence of B. breve. Moreover, C. albicans-induced IL-17 production was decreased after pre-incubation with both Bifidobacterium or Lactobacillus probiotic strains. Whereas C. albicans induced cytokines are dampened by the tested probiotic strains, TNFα and IL-6 production by pure pattern-recognition receptor ligands are potentiated. Interestingly, an important role of Toll-like receptor 9 signalling that involves JNK kinase in the modulatory effects of these probiotic strains has been identified. In conclusion, specific probiotic strains exhibit cross-tolerance effects towards other inflammatory stimuli, especially C. albicans, which might have beneficial effects on gut inflammation.
authors.affiliation: Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Theo S
authors.initials: TS
authors.lastname: Plantinga
authors.forename: Jeroen
authors.initials: J
authors.lastname: van Bergenhenegouwen
authors.forename: Cor
authors.initials: C
authors.lastname: Jacobs
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.forename: Belinda
authors.initials: B
authors.lastname: van't Land
authors.forename: Johan
authors.initials: J
authors.lastname: Garssen
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
mesh_terms: D001644:Bifidobacterium / Q000502:physiology; D002176:Candida albicans / Q000187:drug effects / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D042541:Intracellular Space / Q000187:drug effects / Q000201:enzymology; D007780:Lacticaseibacillus casei / Q000502:physiology; D052201:Lacticaseibacillus rhamnosus / Q000502:physiology; D008024:Ligands; D053473:Nod2 Signaling Adaptor Protein / Q000172:deficiency / Q000378:metabolism; D019936:Probiotics / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000378:metabolism; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008024:Ligands; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D047428:Protein Kinase Inhibitors; D051192:Receptors, Pattern Recognition; D051193:Toll-Like Receptors; D011494:Protein Kinases