Immunomodulatory function and in vivo properties of pediococcus pentosaceus OZF, a promising probiotic strain

Some of the important properties of probiotics are the ability to survive during gastrointestinal transit and to modulate the immune functions. The objectives of the reported study were to assess in vivo gastrointestinal survival of orally administered Pediococcus pentosaceus OZF using an animal model BALB/c mice, and to examine its effects on the immune response. Following oral administration to mice, the ability of Pediococcus pentosaceus OZF to pass and survive through the mouse gastrointestinal system was investigated by analyzing the recovery of the strain in fecal samples. Microbiological and polymerase chain reaction (PCR) methods proved that the strain OZF could overcome specific conditions in the gastrointestinal tract of mice and reach the intestine alive after ingestion. To observe the effect of oral administration on immune response, IL-6, IL-12 and IFN-γ were measured by ELISA, and the strain OZF was found to cause increases in IL-6 synthesis in regularly fed mice. However, stimulation was carried out with various concentrations of bacterial ssDNA and heat killed cells of Pediococcus pentosaceus OZF. The heat killed cells of the strain OZF were shown to produce IFN- γ independently from IL-12. On the other hand, a significant difference between control and experimental group was noticed when lipopolysaccharide, a TLR4 (toll like receptor) ligand, was used. Overall, Pediococcus pentosaceus OZF may be a valuable probiotic strain for therapeutic uses. Nevertheless, further studies on the mechanisms of immunomodulatory effect will allow for better clarification of the immune functions of this strain. © Springer-Verlag Berlin Heidelberg and the University of Milan 2012

Circulating LL37 targets plasma extracellular vesicles to immune cells and intensifies Behçet's disease severity

Behçet's disease (BD) activity is characterised by sustained, over-exuberant immune activation, yet the underlying mechanisms leading to active BD state are poorly defined. Herein, we show that the human cathelicidin derived antimicrobial peptide LL37 associates with and directs plasma extracellular vesicles (EV) to immune cells, thereby leading to enhanced immune activation aggravating BD pathology. Notably, disease activity was correlated with elevated levels of circulating LL37 and EV plasma concentration. Stimulation of healthy PBMC with active BD patient EVs induced heightened IL1β, IFNα, IL6 and IP10 secretion compared to healthy and inactive BD EVs. Remarkably, when mixed with LL37, healthy plasma-EVs triggered a robust immune activation replicating the pathology inducing properties of BD EVs. The findings of this study could be of clinical interest in the management of BD, implicating LL37/EV association as one of the major contributors of BD pathogenesis. © 2017 The Author(s)

Immunostimulatory activity of polysaccharide-poly(I:C) nanoparticles

PubMedID: 21459434Immunostimulatory properties of mushroom derived polysaccharides (PS) as stand-alone agents were tested. Next, PS were nanocomplexed with polyI:C (pIC) to yield stable nanoparticles around 200 nm in size evidenced by atomic force microscopy and dynamic light scattering analyses. PSs were selectively engaged by cells expressing TLR2 and initiated NF?B dependent signaling cascade leading to a Th1-biased cytokine/chemokine secretion in addition to bactericidal nitric oxide (NO) production from macrophages. Moreover, cells treated with nanoparticles led to synergistic IL6, production and upregulation of TNF?, MIP3?, IFN? and IP10 transcript expression. In mice, PS-Ovalbumin-pIC formulation surpassed anti-OVA IgG responses when compared to either PS-OVA or pIC-OVA mediated immunity. Our results revealed that signal transduction initiated both by TLR2 and TLR3 via co-delivery of pIC by PS in nanoparticle depot delivery system is an effective immunization strategy. The present work implicate that the PS and nucleic acid based nanoparticle approach along with protein antigens can be harnessed to prevent infectious diseases. © 2011 Elsevier Ltd.203953 036615 108S316This work was supported by the Scientific and Technological Research Council of Turkey (TÜBİTAK, Grant No: 108S316 ). IG received grant support from EU/FP6/MC IRG (Grant # 036615 ) and EU 7th Framework Project UNAM-Regpot (Grant # 203953 ). GT and FCY received scholarship grants from SANTEZ ( 0448-STZ-2009-2 ) and TUBITAK . We thank to Dr. Aykutlu Dana and his group members for their invaluable support during AFM studies. Drs. Can K. Akcali and Mayda Gursel are sincerely acknowledged for their critical reading of the manuscript. Appendi

CpG ODN nanorings induce IFNα from plasmacytoid dendritic cells and demonstrate potent vaccine adjuvant activity

CpG oligodeoxynucleotides (ODN) are short single-stranded synthetic DNA molecules that activate the immune system and have been found to be effective for preventing and treating infectious diseases, allergies, and cancers. Structurally distinct classes of synthetic ODN expressing CpG motifs differentially activate human immune cells. K-type ODN (K-ODN), which have progressed into human clinical trials as vaccine adjuvants and immunotherapeutic agents, are strong activators of B cells and trigger plasmacytoid dendritic cells (pDCs) to differentiate and produce tumor necrosis factor-α (TNFα). In contrast, D-type ODN (D-ODN) stimulate large amounts of interferon-α (IFNα) secretion from pDCs. This activity depends on the ability of D-ODN to adopt nanometer-sized G quadruplex-based structures, complicating their manufacturing and hampering their progress into the clinic. In search of a D-ODN substitute, we attempted to multimerize K-ODN into stable nanostructures using cationic peptides. We show that short ODN with a rigid secondary structure form nuclease-resistant nanorings after condensation with the HIV-derived peptide Tat(47-57). The nanorings enhanced cellular internalization, targeted the ODN to early endosomes, and induced a robust IFNα response from human pDCs. Compared to the conventional K-ODN, nanorings boosted T helper 1-mediated immune responses in mice immunized with the inactivated foot and mouth disease virus vaccine and generated superior antitumor immunity when used as a therapeutic tumor vaccine adjuvant in C57BL/6 mice bearing ovalbumin-expressing EG.7 thymoma tumors. These results suggest that the nanorings can act as D-ODN surrogates and may find a niche for further clinical applications

Search for displaced muonic lepton jets from light Higgs boson decay in proton-proton collisions at s=7\sqrt{s}=7 TeV with the ATLAS detector

A search is performed for collimated muon pairs displaced from the primary vertex produced in the decay of long-lived neutral particles in proton-proton collisions at sqrt(s) = 7 TeV centre-of-mass energy, with the ATLAS detector at the LHC. In a 1.9 fb-1 event sample collected during 2011, the observed data are consistent with the Standard Model background expectations. Limits on the product of the production cross section and the branching ratio of a Higgs boson decaying to hidden-sector neutral long-lived particles are derived as a function of the particles' mean lifetime