title: Immunomodulatory properties of Streptococcus and Veillonella isolates from the human small intestine microbiota.
abstract: The human small intestine is a key site for interactions between the intestinal microbiota and the mucosal immune system. Here we investigated the immunomodulatory properties of representative species of commonly dominant small-intestinal microbial communities, including six streptococcal strains (four Streptococcus salivarius, one S. equinus, one S. parasanguinis) one Veillonella parvula strain, one Enterococcus gallinarum strain, and Lactobacillus plantarum WCFS1 as a bench mark strain on human monocyte-derived dendritic cells. The different streptococci induced varying levels of the cytokines IL-8, TNF-α, and IL-12p70, while the V. parvula strain showed a strong capacity to induce IL-6. E. gallinarum strain was a potent inducer of cytokines and TLR2/6 signalling. As Streptococcus and Veillonella can potentially interact metabolically and frequently co-occur in ecosystems, immunomodulation by pair-wise combinations of strains were also tested for their combined immunomodulatory properties. Strain combinations induced cytokine responses in dendritic cells that differed from what might be expected on the basis of the results obtained with the individual strains. A combination of (some) streptococci with Veillonella appeared to negate IL-12p70 production, while augmenting IL-8, IL-6, IL-10, and TNF-α responses. This suggests that immunomodulation data obtained in vitro with individual strains are unlikely to adequately represent immune responses to mixtures of gut microbiota communities in vivo. Nevertheless, analysing the immune responses of strains representing the dominant species in the intestine may help to identify immunomodulatory mechanisms that influence immune homeostasis.
authors.affiliation: Top Institute Food and Nutrition (TIFN), Wageningen, The Netherlands; Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Bartholomeus
authors.initials: B
authors.lastname: van den Bogert
authors.affiliation: Host-Microbe Interactomics Group, Wageningen University, Wageningen, The Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: Meijerink
authors.affiliation: Top Institute Food and Nutrition (TIFN), Wageningen, The Netherlands; Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Erwin G
authors.initials: EG
authors.lastname: Zoetendal
authors.affiliation: Host-Microbe Interactomics Group, Wageningen University, Wageningen, The Netherlands.
authors.forename: Jerry M
authors.initials: JM
authors.lastname: Wells
authors.affiliation: Top Institute Food and Nutrition (TIFN), Wageningen, The Netherlands; Host-Microbe Interactomics Group, Wageningen University, Wageningen, The Netherlands; NIZO Food Research B.V., Ede, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: Kleerebezem
mesh_terms: D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D056747:Immunomodulation / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D007421:Intestine, Small / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000382:microbiology; D064307:Microbiota / Q000235:genetics / Q000276:immunology; D013291:Streptococcus / Q000276:immunology* / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D014678:Veillonella / Q000276:immunology* / Q000472:pathogenicity
chemical_list: C508609:IL10 protein, human; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12