Limits...
Immunomodulatory properties of Streptococcus and Veillonella isolates from the human small intestine microbiota.

van den Bogert B, Meijerink M, Zoetendal EG, Wells JM, Kleerebezem M - PLoS ONE (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Top Institute Food and Nutrition (TIFN), Wageningen, The Netherlands; Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.

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.

Show MeSH

Related in: MedlinePlus

Cytokine secretion by dendritic cells after mono-stimulation with bacterial strains, disrupted strains, and spent medium.Dendritic cells were derived from monocytes from 2 human donors. Spent medium was tested with or without LPS.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4257559&req=5

pone-0114277-g003: Cytokine secretion by dendritic cells after mono-stimulation with bacterial strains, disrupted strains, and spent medium.Dendritic cells were derived from monocytes from 2 human donors. Spent medium was tested with or without LPS.

Mentions: As the S. equinus strain elicited a low immune response compared to the other strains tested (Figure 2), we hypothesized that this strain might possess an immunomodulatory component that suppresses cytokine secretion. Therefore, we co-stimulated DCs with LPS (10 ng/ml) and S. equinus or S. salivarius strain 4. A lower LPS dose was used (10 ng/mL) compared to the previous immune assay (mono-stimulations) to be able to modulate the cytokines response. S. salivarius strain 4 was chosen as a control strain because it induced considerable cytokine production in dendritic cells. Moreover, the genomic lineage that this strain belongs to was highly predominant in ileostoma effluent and appears to be among the genomic lineage that is ubiquitously found in the human small intestine, supporting the relevance of selecting this strain for comparative reasons [29], [30]. The S. equinus strain did not significantly modulate the cytokine levels induced by LPS stimulation. Nevertheless, the amount of IL-6 produced by DCs stimulated with S. equinus and LPS together, was higher than the sum of the levels induced by the two separate stimuli, suggesting that these stimuli may synergistically induce the secretion of this cytokine by DCs rather than the hypothesized immunosuppressive effect of S. equinus. A qualitatively similar and quantitatively significant synergistic effect on IL-6 production was also observed when DCs were co-stimulated with S. salivarius and LPS (Figure 3). Co-stimulation of DCs with LPS and spent culture supernatant from either of the two bacterial strains also consistently elevated production of most cytokines (except for TNF-α) as compared to LPS alone (Figure 3), although this effect was not significant and appeared to be smaller as compared to the co-stimulation by the bacterial cells.


Immunomodulatory properties of Streptococcus and Veillonella isolates from the human small intestine microbiota.

van den Bogert B, Meijerink M, Zoetendal EG, Wells JM, Kleerebezem M - PLoS ONE (2014)

Cytokine secretion by dendritic cells after mono-stimulation with bacterial strains, disrupted strains, and spent medium.Dendritic cells were derived from monocytes from 2 human donors. Spent medium was tested with or without LPS.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4257559&req=5

pone-0114277-g003: Cytokine secretion by dendritic cells after mono-stimulation with bacterial strains, disrupted strains, and spent medium.Dendritic cells were derived from monocytes from 2 human donors. Spent medium was tested with or without LPS.
Mentions: As the S. equinus strain elicited a low immune response compared to the other strains tested (Figure 2), we hypothesized that this strain might possess an immunomodulatory component that suppresses cytokine secretion. Therefore, we co-stimulated DCs with LPS (10 ng/ml) and S. equinus or S. salivarius strain 4. A lower LPS dose was used (10 ng/mL) compared to the previous immune assay (mono-stimulations) to be able to modulate the cytokines response. S. salivarius strain 4 was chosen as a control strain because it induced considerable cytokine production in dendritic cells. Moreover, the genomic lineage that this strain belongs to was highly predominant in ileostoma effluent and appears to be among the genomic lineage that is ubiquitously found in the human small intestine, supporting the relevance of selecting this strain for comparative reasons [29], [30]. The S. equinus strain did not significantly modulate the cytokine levels induced by LPS stimulation. Nevertheless, the amount of IL-6 produced by DCs stimulated with S. equinus and LPS together, was higher than the sum of the levels induced by the two separate stimuli, suggesting that these stimuli may synergistically induce the secretion of this cytokine by DCs rather than the hypothesized immunosuppressive effect of S. equinus. A qualitatively similar and quantitatively significant synergistic effect on IL-6 production was also observed when DCs were co-stimulated with S. salivarius and LPS (Figure 3). Co-stimulation of DCs with LPS and spent culture supernatant from either of the two bacterial strains also consistently elevated production of most cytokines (except for TNF-α) as compared to LPS alone (Figure 3), although this effect was not significant and appeared to be smaller as compared to the co-stimulation by the bacterial cells.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Top Institute Food and Nutrition (TIFN), Wageningen, The Netherlands; Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.

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.

Show MeSH
Related in: MedlinePlus