title: Lactobacillus rhamnosus GG Activation of Dendritic Cells and Neutrophils Depends on the Dose and Time of Exposure.
abstract: This study evaluates the ability of Lactobacillus rhamnosus GG (LGG) to activate DC and neutrophils and modulate T cell activation and the impact of bacterial dose on these responses. Murine bone marrow derived DC or neutrophils were stimulated with LGG at ratios of 5 : 1, 10 : 1, and 100 : 1 (LGG : cells) and DC maturation (CD40, CD80, CD86, CD83, and MHC class II) and cytokine production (IL-10, TNF-α, and IL-12p70) were examined after 2 h and 18 h coculture and compared to the ability of BCG (the present immunotherapeutic agent for bladder cancer) to stimulate these cells. A 2 h exposure to 100 : 1 (high dose) or an 18 h exposure to 5 : 1 or 10 : 1 (low dose), LGG : cells, induced the highest production of IL-12 and upregulation of CD40, CD80, CD86, and MHC II on DC. In DCs stimulated with LGG activated neutrophils IL-12 production decreased with increasing dose. LGG induced 10-fold greater IL-12 production than BCG. T cell IFNγ and IL-2 production was significantly greater when stimulated with DC activated with low dose LGG. In conclusion, DC or DC activated with neutrophils exposed to low dose LGG induced greater Th1 polarization in T cells and this could potentially exert stronger antitumor effects. Thus the dose of LGG used for immunotherapy could determine treatment efficacy.
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228.
authors.forename: Shirong
authors.identifier: 0000-0002-0650-2234
authors.initials: S
authors.lastname: Cai
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228.
authors.forename: Matheswaran
authors.identifier: 0000-0001-7734-4600
authors.initials: M
authors.lastname: Kandasamy
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228.
authors.forename: Juwita N
authors.identifier: 0000-0003-4134-0434
authors.initials: JN
authors.lastname: Rahmat
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228.
authors.forename: Sin Mun
authors.identifier: 0000-0001-5136-2894
authors.initials: SM
authors.lastname: Tham
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594.
authors.forename: Boon Huat
authors.initials: BH
authors.lastname: Bay
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545.
authors.forename: Yuan Kun
authors.identifier: 0000-0001-8214-9666
authors.initials: YK
authors.lastname: Lee
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228.
authors.forename: Ratha
authors.identifier: 0000-0002-4359-2160
authors.initials: R
authors.lastname: Mahendran
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D016130:Immunophenotyping; D052201:Lacticaseibacillus rhamnosus / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018375:Neutrophil Activation / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D000954:Antigens, Surface; D016207:Cytokines