Article

Escherichia coli Nissle 1917 distinctively modulates T-cell cycling and expansion via toll-like receptor 2 signaling.

Department of Hepatology and Gastroenterology, Campus Virchow Clinic, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany.
Infection and Immunity (Impact Factor: 4.16). 04/2005; 73(3):1452-65. DOI: 10.1128/IAI.73.3.1452-1465.2005
Source: PubMed

ABSTRACT Although the probiotic Escherichia coli strain Nissle 1917 has been proven to be efficacious for the treatment of inflammatory bowel diseases, the underlying mechanisms of action still remain elusive. The aim of the present study was to analyze the effects of E. coli Nissle 1917 on cell cycling and apoptosis of peripheral blood and lamina propria T cells (PBT and LPT, respectively). Anti-CD3-stimulated PBT and LPT were treated with E. coli Nissle 1917-conditioned medium (E. coli Nissle 1917-CM) or heat-inactivated E. coli Nissle 1917. Cyclin B1, DNA content, and caspase 3 expression were measured by flow cytometry to assess cell cycle kinetics and apoptosis. Protein levels of several cell cycle and apoptosis modulators were determined by immunoblotting, and cytokine profiles were determined by cytometric bead array. E. coli Nissle 1917-CM inhibits cell cycling and expansion of peripheral blood but not mucosal T cells. Bacterial lipoproteins mimicked the effect of E. coli Nissle 1917-CM; in contrast, heat-inactivated E. coli Nissle 1917, lipopolysaccharide, or CpG DNA did not alter PBT cell cycling. E. coli Nissle 1917-CM decreased cyclin D2, B1, and retinoblastoma protein expression, contributing to the reduction of T-cell proliferation. E. coli Nissle 1917 significantly inhibited the expression of interleukin-2 (IL-2), tumor necrosis factor alpha, and gamma interferon but increased IL-10 production in PBT. Using Toll-like receptor 2 (TLR-2) knockout mice, we further demonstrate that the inhibition of PBT proliferation by E. coli Nissle 1917-CM is TLR-2 dependent. The differential reaction of circulating and tissue-bound T cells towards E. coli Nissle 1917 may explain the beneficial effect of E. coli Nissle 1917 in intestinal inflammation. E. coli Nissle 1917 may downregulate the expansion of newly recruited T cells into the mucosa and limit intestinal inflammation, while already activated tissue-bound T cells may eliminate deleterious antigens in order to maintain immunological homeostasis.

0 Bookmarks
 · 
122 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: To reduce medication for patients with ulcerative colitis (UC), we need to establish the etiology of UC. The intestinal microbiota of patients with inflammatory bowel disease (IBD) has been shown to differ from that of healthy controls and abundant data indicate that it changes in both composition and localization. Small intestinal bacterial overgrowth is significantly higher in IBD patients compared with controls. Probiotics have been investigated for their capacity to reduce the severity of UC. The luminal surfaces of the gastrointestinal tract are covered by a mucus layer. This normally acts as a barrier that does not allow bacteria to reach the epithelial cells and thus limits the direct contact between the host and the bacteria. The mucus layer in the colon comprises an inner layer that is firmly adherent to the intestinal mucosa, and an outer layer that can be washed off with minimal rinsing. Some bacteria can dissolve the protective inner mucus layer. Defects in renewal and formation of the inner mucus layer allow bacteria to reach the epithelium and have implications for the causes of colitis. In this review, important elements of UC pathology are thought to be the intestinal bacteria, gut mucus, and the mucosa-associated immune system.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The objective of this study was to assess the effect of orally administered Escherichia coli Nissle 1917 (EcN) on the jejunal health of weaned piglets that were unchallenged or challenged with porcine enterotoxigenic Escherichia coli Abbottstown (EcA). A total of 40 weaned Landrace × Yorkshire piglets (5.83 ± 0.24 kg) were allocated to 4 groups with 10 barrows per group, following a 2 × 2 factorial design with 2 inclusion levels of EcN (daily oral administration of 2 mL sterile water or 2 mL EcN (109 cells/mL)) at 10:00 h) and 2 inclusion levels of EcA (daily oral administration of 2 mL sterile water or 2 mL EcA (109 cells/mL) at 14:00 h). Thus, there were four treatments: 1) control diet (C); 2) C + EcN (N); 3) C + EcA (A); 4) C+ EcN + EcA (N + A). This experiment lasted for 21 days. The results indicated a significant interaction between EcN and EcA on growth performance and jejunal mucosal membrane integrity, morphology, immune parameters and the antioxidant capacity in 21-day-weaned piglets (P < 0.05). The results that piglets in the A group had lowest feed conversion, daily weight gain, daily feed intake, jejunal villus height (P < 0.05) among the 4 groups suggested that the oral administration of EcA decreased growth performance. The results that piglets in the A group had lowest mRNA levels of regenerating islet derived protein 3 gamma and transforming growth factor beta 1 (P < 0.05), lowest protein levels of claudin-1, occludin, and zonula occludens -1 (P < 0.05) and highest serum d-lactate concentration (P < 0.05) among the 4 groups suggested that the oral administration of EcA damaged jejunal mucosal membrane integrity. The immune and antioxdant parameters results that orally administered EcA increased mRNA levels of interleukin (IL)-1β, IL-8, tumor necrosis factor (TNF)-α, and toll-like receptor (TLR) -4 (P < 0.05), increased the concentrations of IgM, IgG, IL-1β, TNF-α, sIgA (P < 0.05), and TLR-4, and decreased activities of superoxide dismutase and total antioxidant (P < 0.05) suggested that EcA could make the jejunal mucosal membrane inflamed in early weaned piglets. Orally administered EcN tended to improved growth performance, jejunal villus height, the immune and antioxdant function, jejunal mucosal membrane integrity in piglet unchallenged or challenged with EcA. This improvement of the jejunal health and growth performance of piglets challenged with EcA by oral administration of EcN could be attributed to increased defense against harmful bacteria and improved epithelial barrier function. These results demonstrated that EcN could be used in early-weaned piglets to prevent intestinal infection by the pathogenic bacteria EcA.
    Animal Feed Science and Technology 10/2014; DOI:10.1016/j.anifeedsci.2014.10.011 · 2.09 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recombinant subunit vaccine engineering increasingly focuses on the development of more effective delivery platforms. However, current recombinant vaccines fail to sufficiently stimulate protective adaptive immunity against a wide range of pathogens while remaining a cost effective solution to global health challenges. Taking an unorthodox approach to this fundamental immunological challenge, we isolated the TLR-targeting capability of the probiotic E. coli Nissle 1917 bacteria (EcN) by engineering bionanoparticlate antigen carriers derived from EcN outer membrane vesicles (OMVs). Exogenous model antigens expressed by these modified bacteria as protein fusions with the bacterial enterotoxin ClyA resulted in their display on the surface of the carrier OMVs. Vaccination with the engineered EcN OMVs in a BALB/c mouse model, and subsequent mechanism of action analysis, established the EcN OMV's ability to induce self-adjuvanted robust and protective humoral and TH1-biased cellular immunity to model antigens. This finding appears to be strain-dependent, as OMV antigen carriers similarly engineered from a standard K12 E. coli strain derivative failed to generate a comparably robust antigen-specific TH1 bias. The results demonstrate that unlike traditional subunit vaccines, these biomolecularly engineered "pathogen-like particles" derived from traditionally overlooked, naturally potent immunomodulators have the potential to effectively couple recombinant antigens with meaningful immunity in a broadly applicable fashion.
    PLoS ONE 11/2014; 9(11):e112802. DOI:10.1371/journal.pone.0112802 · 3.53 Impact Factor

Preview

Download
1 Download
Available from