Immune Response to Bifidobacterium bifidum Strains Support Treg/Th17 Plasticity

Abstract

In this work we analyzed the immune activation properties of different Bifidobacterium strains in order to establish their ability as inductors of specific effector (Th) or regulatory (Treg) responses. First, we determined the cytokine pattern induced by 21 Bifidobacterium strains in peripheral blood mononuclear cells (PBMCs). Results showed that four Bifidobacterium bifidum strains showed the highest production of IL-17 as well as a poor secretion of IFNγ and TNFα, suggesting a Th17 profile whereas other Bifidobacterium strains exhibited a Th1-suggestive profile. Given the key role of Th17 subsets in mucosal defence, strains suggestive of Th17 responses and the putative Th1 Bifidobacterium breve BM12/11 were selected to stimulate dendritic cells (DC) to further determine their capability to induce the differentiation of naïve CD4+ lymphocytes toward different Th or Treg cells. All selected strains were able to induce phenotypic DC maturation, but showed differences in cytokine stimulation, DC treated with the putative Th17 strains displaying high IL-1β/IL-12 and low IL-12/IL-10 index, whereas BM12/11-DC exhibited the highest IL-12/IL-10 ratio. Differentiation of naïve lymphocytes confirmed Th1 polarization by BM12/11. Unexpectedly, any B. bifidum strain showed significant capability for Th17 generation, and they were able to generate functional Treg, thus suggesting differences between in vivo and vitro responses. In fact, activation of memory lymphocytes present in PBMCS with these bacteria, point out the presence in vivo of specific Th17 cells, supporting the plasticity of Treg/Th17 populations and the key role of commensal bacteria in mucosal tolerance and T cell reprogramming when needed.

Safety ofBifidobacterium animalissubsp.lactis(B. lactis) strain BB-12-supplemented yogurt in healthy adults on antibiotics: a phase I safety study

“…Significant changes in gene expression were detected at day 14 after the intervention was interrupted for 3 d. Notably, GATA3, a transcription factor involved in the early differentiation and T-cell lineage commitment, 17 CD80 a transmembrane receptor associated with antigen recognition, 18 and CXCL10, a chemokine involved in early cell stimulation, were upregulated at least fivefold only in blood of participants from the B. lactis-supplemented yogurt group (P < 0.05). A fivefold induction of tumor necrosis factor a (TNFA) expression in response to BB-12 supplementation is suggestive of a Th1 polarization effect as previously shown in in vitro culture experiments with isolated human peripheral blood mononuclear cells (PBMC), 14,19 indicating a direct activation of blood monocytes, as well as T lymphocytes toward a mild inflammatory Th1 response ( Table 4).…”

Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity

“…For example, Streptococcus parasanguinis and Streptococcus australis were associated with IFNγ production, but other species such as the Streptococcus mitis/ oralis/pneumoniae group were associated with IL-1β. Examples of a microbial species predicted to affect multiple cytokines (IP1) include Bifidobacterium, which has been previously associated with IFNγ production (Lopez et al, 2011;Menard et al, 2008). Here, we observed a positive correlation between Bifidobacterium pseudocatenulatum and IFNγ.…”

Exploring the role of the microbiota member Bifidobacterium in modulating immune-linked diseases

“…A significant complication in evaluating these responses lies in the fact that many distinct species and strains of bifidobacteria have been tested, and additionally many of these studies include combination testing with other species or phylum. Furthermore, the cell type, species of animal, model used, and human cohort supplemented also affect immune responses generated [39]. Currently, most mechanistic studies have focused on inflammatory bowel disease (IBD) (Figure 2), allergy, and infection models, reporting bifidobacterial-associated modulation of specific immune cells and their outputs.…”