Postbiotics: what else? Tsilingiri, K; Rescigno, M
Beneficial microbes,
03/2013, Letnik:
4, Številka:
1
Journal Article
Recenzirano
The use of probiotics and synbiotics in the food industry or as food supplements for a balanced diet and improved gut homeostasis has been blooming for the past decade. As feedback from healthy ...consumers is rather enthusiastic, a lot of effort is currently directed in elucidating the mechanisms of interaction between beneficial microbes and barrier and immune function of the host. The use of probiotics or synbiotics for treating certain pathologies has also been examined, however, the outcome has not always been favourable. In most cases, the effect of the administered probiotic is evident when the bacteria are still alive at the time they reach the small and large intestine, suggesting that it is dependent on the metabolic activity of the bacteria. Indeed, in some occasions it has been shown that the culture supernatant of these bacteria mediates the immunomodulatory effect conferred to the host. Recent work on relevant probiotic strains has also led to the isolation and characterisation of certain probiotic-produced, soluble factors, here called postbiotics, which were sufficient to elicit the desired response. Here, we summarise these recent findings and propose the use of purified and well characterised postbiotic components as a safer alternative for clinical applications, especially in chronic inflammatory conditions like inflammatory bowel disease, where probiotics have not yet given encouraging results as far as induction of remission is concerned.
In mice, a subpopulation of gut dendritic cells (DCs) expressing CD103 drives the development of regulatory T (T(reg)) cells. Further, it was recently described that the cross-talk between human ...intestinal epithelial cells (IECs) and DCs helps in maintaining gut immune homeostasis via the induction of non-inflammatory DCs. In this study, an analysis was carried out to determine whether IECs could promote the differentiation of CD103+ tolerogenic DCs, and the function of primary CD103+ DCs isolated from human mesenteric lymph nodes (MLNs) was evaluated.
Monocyte-derived DCs (MoDCs) and circulating CD1c+ DCs were conditioned or not with supernatants from Caco-2 cells or IECs isolated from healthy donors or donors with Crohn's disease and analysed for their ability to induce T(reg) cell differentiation. In some cases, transforming growth factor beta (TGFbeta), retinoic acid (RA) or thymic stromal lymphopoietin (TSLP) were neutralised before conditioning. CD103+ and CD103- DCs were sorted by fluorescence-activated cell sorting (FACS) from MLNs and used in T(reg) cell differentiation experiments.
It was found that human IECs promoted the differentiation of tolerogenic DCs able to drive the development of adaptive Foxp3+ T(reg) cells. This control was lost in patients with Crohn's disease and paralleled a reduced expression of tolerogenic factors by primary IECs. MoDCs differentiated with RA or IEC supernatant upregulated the expression of CD103. Consistently, human primary CD103+ DCs isolated from MLNs were endowed with the ability to drive T(reg) cell differentiation. This subset of DCs expressed CCR7 and probably represents a lamina propria-derived migratory population.
A population of tolerogenic CD103+ DCs was identified in the human gut that probably differentiate in response to IEC-derived factors and drive T(reg) cell development.
Intestinal dendritic cells (DCs) have been shown to display specialized functions, including the ability to promote gut tropism to lymphocytes, to polarize noninflammatory responses, and to drive the ...differentiation of adaptive Foxp3(+) regulatory T (T(reg)) cells. However, very little is known about what drives the mucosal phenotype of DCs. Here, we present evidence that the local microenvironment, and in particular intestinal epithelial cells (ECs), drive the differentiation of T(reg)-cell-promoting DCs, which counteracts Th1 and Th17 development. EC-derived transforming growth factor-beta (TGF-beta) and retinoic acid (RA), but not thymic stromal lymphopoietin (TSLP), were found to be required for DC conversion. After EC contact, DCs upregulated CD103 and acquired a tolerogenic phenotype. EC-conditioned DCs were capable of inducing de novo T(reg) cells with gut-homing properties that when adoptively transferred, protected mice from experimental colitis. Thus, we have uncovered an essential mechanism in which EC control of DC function is required for tolerance induction.
CD103(+) gut dendritic cells (DCs) have been shown to be required for de novo conversion of adaptive T regulatory (Treg) cells. Indoleamine 2,3-dioxygenase (IDO) is an enzyme involved in tryptophan ...catabolism that is expressed by DCs isolated from tumour-draining lymph nodes. IDO-expressing DCs sustain and differentiate Tregs. The aim of this study was to investigate the expression and the possible physiological role of IDO in the tolerogenic properties of intestinal DCs.
The expression level of IDO in CD103(+) and CD103(-) DCs was analysed by qRT-PCR, western blot and immunofluorescence. CD103(+) and CD103(-) DCs were sorted from mesenteric lymph nodes (MLNs) and the small intestinal lamina propria, and the role of IDO in the conversion of Tregs and Th effector cell development was evaluated via specific inhibition or gene deletion. Oral tolerance, experimental colitis and T cell differentiation in vivo were assessed upon IDO inactivation.
We show that, primarily, CD103(+) but not CD103(-) gut DCs express IDO whose inhibition results in reduced CD4(+)Foxp3(+) T regulatory cell conversion and enhanced T cell proliferation. When IDO was inhibited or genetically deleted there was an increase in Th1 and Th17 differentiation both in vitro and in vivo. Finally, in vivo IDO blockade affected the development of Tregs specific for orally administered antigens, impaired oral tolerance induction and exacerbated colitis.
We identified a new IDO-dependent pathway leading to acquisition of tolerogenic functions in mucosal CD103-expressing DCs, indicating IDO as a possible therapeutic target for gut disorders.
Solid mixtures of ammonia and water, the so-called ammonia hydrates, are thought to be major components of solar and extra-solar icy planets. We present here a thorough characterization of the ...recently reported high pressure (P)–temperature (T) phase VII of ammonia monohydrate (AMH) using Raman spectroscopy, X-ray diffraction, and quasi-elastic neutron scattering (QENS) experiments in the ranges 4–10 GPa, 450–600 K. Our results show that AMH-VII exhibits common structural features with the disordered ionico-molecular alloy (DIMA) phase, stable above 7.5 GPa at 300 K: both present a substitutional disorder of water and ammonia over the sites of a body-centered cubic lattice and are partially ionic. The two phases however markedly differ in their hydrogen dynamics, and QENS measurements show that AMH-VII is characterized by free molecular rotations around the lattice positions which are quenched in the DIMA phase. AMH-VII is thus a peculiar crystalline solid in that it combines three types of disorder: substitutional, compositional, and rotational.
Thymic stromal lymphopoietin (TSLP) is produced by epithelial cells and keratinocytes, and is involved in immune homeostasis or inflammation. The mechanism through which TSLP regulates intestinal ...inflammation is unclear. Here, we report that mouse dendritic cells (DCs) express TSLP both in vitro and in vivo in response to Toll-like receptor ligation in a MyD88-dependent fashion. TSLP is produced by the CD103(+) subset of tolerogenic gut DCs and is downregulated during experimental colitis. TSLP produced by DCs acts directly on T cells by reducing their capacity to produce interleukin (IL)-17 and fostering the development of Foxp3(+) T cells. Consistently, TSLP protects against colitis development through a direct action on T cells, as adoptive transfer of naïve T cells from TSLPR(-/-) to SCID mice results in a more severe colitis, with increased frequency of IL-17-producing T cells and inflammatory cytokines. Hence, we describe a new anti-inflammatory role of TSLP in the gut.
SiPM-based readouts are becoming the standard for light detection in particle detectors given their superior resolution and ease of use with respect to vacuum tube photo-multipliers. However, the ...contributions of noise detection such as the dark rate, cross-talk, and after-pulsing (AP) may significantly impact their performance. In this work, we present the development of highly reflective single-phase argon chambers capable of displaying light yields up to 32 photo-electrons per keV, with approximately 12 being primary photo-electrons generated by the argon scintillation, while the rest are accounted by optical cross-talk. Furthermore, the presence of compound processes results in a generalized Fano factor larger than 2 already at an over-voltage of 5 V. Finally, we present a parametrization of the optical cross-talk for the FBK NUV-HD-Cryo SiPMs at 87 K that can be extended to future detectors with tailored optical simulations.
In this study, we aimed to investigate some functional characteristics and the immunomodulatory properties of three strains of Lactobacillus plantarum of dairy origin which, in a previous screening, ...showed to be candidate probiotics. Genome sequencing and comparative genomics, which confirmed the presence of genes involved in folate and riboflavin production and in the immune response of dendritic cells (DCs), prompted us to investigate the ability of the three strains to accumulate the two vitamins and their immunomodulation properties. The ability of the three strains to release antioxidant components in milk was also investigated. Small amounts of folate and riboflavin were produced by the three strains, while they showed a good antioxidant capacity in milk with FRAP method. The immune response experiments well correlated with the presence of candidate genes influencing in DCs cytokine response to L. plantarum. Specifically, the amounts of secreted cytokins by DCs after stimulation with cells of Lp790, Lp813 and Lp998 resulted pro-inflammatory whereas stimulation with culture supernatants (postbiotics) inhibited the release of interleukin (IL)-12p70 and increased the release of the anti-inflammatory IL-10 cytokine. This study adds further evidence on the importance of L. plantarum in human health. Understanding how probiotics (or postbiotics) work in preclinical models can allow a rational choice of the different strains for clinical and/or commercial use.
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