Human cornea-derived mesenchymal stromal cells inhibit T cells through indoleamine 2,3 dioxygenase.

Defining the mechanism of immune modulation by mesenchymal stromal cells (MSCs) from distinct anatomical tissues is of great translational interest. The human cornea is an immunologically privileged organ, and the mechanism of immunoregulation of cornea-derived MSCs (cMSCs) is currently unknown. We investigated cMSCs derived from the corneas of 5 independent human donorS for their fitness and mechanism of action in suppressing T cells.

Vascular endothelial growth factor secretion and immunosuppression are distinct potency mechanisms of human bone marrow mesenchymal stromal cells.

Mesenchymal stromal cells (MSCs) are investigated as cellular therapeutics for inflammatory bowel diseases and associated perianal fistula, although consistent efficacy remains a concern. Determining host factors that modulate MSCs' potency including their secretion of angiogenic and wound-healing factors, immunosuppression, and anti-inflammatory properties are important determinants of their functionality. We investigated the mechanisms that regulate the secretion of angiogenic and wound-healing factors and immune suppression of human bone marrow MSCs.

Molecular cloning, overexpression, characterization, and In silico modelling analysis of a novel GDSL autotransporter-dependent outer membrane lipase (OML) of Pseudomonas guariconensis.

The outer membrane lipase (oml) gene, encoding a novel autotransporter-dependent lipase from Pseudomonas guariconensis, was cloned and sequenced. The oml gene has an open reading frame of 1866 bp. It encodes the 621 amino acid autotransporter-dependent GDSL lipase (OML), which has the highest sequence similarity (64.

Effects of Atrazine exposure on human bone marrow-derived mesenchymal stromal cells assessed by combinatorial assay matrix.

Introduction: Mesenchymal Stromal/Stem cells (MSCs) are an essential component of the regenerative and immunoregulatory stem cell compartment of the human body and thus of major importance in human physiology. The MSCs elicit their beneficial properties through a multitude of complementary mechanisms, which makes it challenging to assess their phenotype and function in environmental toxicity screening. We here employed the novel combinatorial assays matrix approach/technology to profile the MSC response to the herbicide Atrazine, which is a common environmental xenobiotic, that is in widespread agricultural use in the US and other countries, but banned in the EU.

Contrariety of Human Bone Marrow Mesenchymal Stromal Cell Functionality in Modulating Circulatory Myeloid and Plasmacytoid Dendritic Cell Subsets.

Mesenchymal Stromal Cells (MSCs) derived from bone marrow are widely tested in clinical trials as a cellular therapy for potential inflammatory disorders. The mechanism of action of MSCs in mediating immune modulation is of wide interest. In the present study, we investigated the effect of human bone-marrow-derived MSCs in modulating the circulating peripheral blood dendritic cell responses through flow cytometry and multiplex secretome technology upon their coculture ex vivo.

Conglomeration of T- and B-Cell Matrix Responses Determines the Potency of Human Bone Marrow Mesenchymal Stromal Cells.

Cell manufacturing facilities need to define the potency of mesenchymal stromal cells (MSCs) as cellular therapeutics in advanced clinical trials or marketing approval. Since MSCs' mechanism of action in humans is not well defined, more than a single functional property of MSCs needs to be captured as a surrogate measure of potency utilizing assay matrix technologies. However, the current limitation is the sole investigation of MSC-mediated T-cell suppression as a surrogate measure of potency.

Chemokine Assay Matrix Defines the Potency of Human Bone Marrow Mesenchymal Stromal Cells.

Potency analysis of mesenchymal stromal cells (MSCs) is required for their use in advanced clinical trials. Assay matrix strategy evaluating more than a single property of MSCs is an emerging strategy in potency analysis. Here we developed an assay matrix approach focusing on the secretory chemokine responses of MSCs using multiplex analytical method.

Hepatocellular Carcinoma Cells Are Protected From Immunolysis by Mesenchymal Stromal Cells Through Indoleamine 2,3 Dioxygenase.

B7 family proteins serve as checkpoint molecules that protect tumors from T cell mediated lysis. Tryptophan degrading enzymes indoleamine 2,3 dioxygenase (IDO) and tryptophan 2,3 dioxygenase (TDO) also induce T cell immune tolerance. However, little is known about the relative contribution of B7 molecules, tryptophan degrading enzymes, as well as the impact of tumor and stromal cell interactions to the development of immunosuppressive tumor microenvironment.

Virulence genes and enterobacterial repetitive intergenic consensus region (ERIC) profiling reveals highly diverse genetic population among avian strains of Pasteurella multocida.

Pasteurella multocida is a multispecies pathogen with certain host specific capsular types but interspecies transmission cannot be overlooked. Knowing the diversity of P. multocida in a geographical location is essential to formulate a vaccination programme.

Heterologous expression of genes for bioconversion of xylose to xylonic acid in Corynebacterium glutamicum and optimization of the bioprocess.

In bacterial system, direct conversion of xylose to xylonic acid is mediated through NAD-dependent xylose dehydrogenase (xylB) and xylonolactonase (xylC) genes. Heterologous expression of these genes from Caulobacter crescentus into recombinant Corynebacterium glutamicum ATCC 13032 and C. glutamicum ATCC 31831 (with an innate pentose transporter, araE) resulted in an efficient bioconversion process to produce xylonic acid from xylose.

Production of low-calorie structured lipids from spent coffee grounds or olive pomace crude oils catalyzed by immobilized lipase in magnetic nanoparticles.

In this study, crude oils extracted from spent coffee grounds (SCG) and olive pomace (OP) were used as raw-material to synthesize low-calorie triacylglycerols, either by acidolysis with capric acid, or by interesterification with ethyl caprate, in solvent-free media, catalyzed by sn-1,3 regioselective lipases. The Rhizopus oryzae lipase (ROL) was immobilized in magnetite nanoparticles (MNP-ROL) and tested as novel biocatalyst. MNP-ROL performance was compared with that of the commercial immobilized Thermomyces lanuginosus lipase (Lipozyme TL IM).

Lipase of Pseudomonas guariconesis as an additive in laundry detergents and transesterification biocatalysts.

A newly isolated culture, Pseudomonas guariconesis, is reported for the first time for lipase production. Various process parameters affecting enzyme production were optimized through statistical design experiments. The Plackett-Burman experimental design was used for screening 10 parameters for lipase production, which was further optimized using the central composite design of response surface methodology.

Valorization of lignocellulosic residues from the olive oil industry by production of lignin, glucose and functional sugars.

Spent olive pomace from the two-phase extraction system of virgin olive oil and olive pomace oil, is a major agro-industrial residue. Present study aimed at the valorization of residual olive pomace and stones (seeds) by hydrothermal treatment and enzymatic hydrolysis of glucans. Both residues contain lignin (31.

The Morphology and Assembly of Respiratory Syncytial Virus Revealed by Cryo-Electron Tomography.

Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract disease in young children. With repeat infections throughout life, it can also cause substantial disease in the elderly and in adults with compromised cardiac, pulmonary and immune systems. RSV is a pleomorphic enveloped RNA virus in the family.

MUC5AC Levels Associated With Respiratory Syncytial Virus Disease Severity.

To assess MUC5AC as a biomarker for respiratory syncytial virus (RSV) disease severity, we tested nasal aspirates from RSV+ children with mild, moderate, and severe disease. Levels were significantly higher in those in the severe and moderate groups compared to mild group, indicating MUC5AC may be a useful biomarker for RSV disease severity.

Infant Viral Respiratory Infection Nasal Immune-Response Patterns and Their Association with Subsequent Childhood Recurrent Wheeze.

Rationale: Recurrent wheeze and asthma are thought to result from alterations in early life immune development following respiratory syncytial virus (RSV) infection. However, prior studies of the nasal immune response to infection have assessed only individual cytokines, which does not capture the whole spectrum of response to infection.

Objectives: To identify nasal immune phenotypes in response to RSV infection and their association with recurrent wheeze.

Protective role of Indoleamine 2,3 dioxygenase in Respiratory Syncytial Virus associated immune response in airway epithelial cells.

RSV is a major cause of severe lower respiratory infection in infants and young children. With no vaccine yet available, it is important to clarify mechanisms of disease pathogenesis. Since indoleamine-2,3-dioxygenase (IDO) is an immunomodulatory enzyme and is upregulated with RSV infection, we studied it in vivo during infection of BALB/c mice and in vitro in A549 cells.

Immune dysfunctionality of replicative senescent mesenchymal stromal cells is corrected by IFNγ priming.

Industrial-scale expansion of mesenchymal stromal cells (MSCs) is often used in clinical trials, and the effect of replicative senescence on MSC functionality is of mechanistic interest. Senescent MSCs exhibit cell-cycle arrest, cellular hypertrophy, and express the senescent marker β-galactosidase. Although both fit and senescent MSCs display intact lung-homing properties in vivo, senescent MSCs acquire a significant defect in inhibiting T-cell proliferation and cytokine secretion in vitro.

Human rhinovirus induced cytokine/chemokine responses in human airway epithelial and immune cells.

Infections with human rhinovirus (HRV) are commonly associated with acute upper and lower respiratory tract disease and asthma exacerbations. The role that HRVs play in these diseases suggests it is important to understand host-specific or virus-specific factors that contribute to pathogenesis. Since species A HRVs are often associated with more serious HRV disease than species B HRVs, differences in immune responses they induce should inform disease pathogenesis.

Response to rhinovirus infection by human airway epithelial cells and peripheral blood mononuclear cells in an in vitro two-chamber tissue culture system.

Human rhinovirus (HRV) infections are associated with the common cold, occasionally with more serious lower respiratory tract illnesses, and frequently with asthma exacerbations. The clinical features of HRV infection and its association with asthma exacerbation suggest that some HRV disease results from virus-induced host immune responses to infection. To study the HRV-infection-induced host responses and the contribution of these responses to disease, we have developed an in vitro model of HRV infection of human airway epithelial cells (Calu-3 cells) and subsequent exposure of human peripheral blood mononuclear cells (PBMCs) to these infected cells in a two-chamber trans-well tissue culture system.

Distinct host cell proteins incorporated by SIV replicating in CD4+ T cells from natural disease resistant versus non-natural disease susceptible hosts.

Background: Enveloped viruses including the simian immunodeficiency virus (SIV) replicating within host cells acquire host proteins upon egress from the host cells. A number of studies have catalogued such host proteins, and a few have documented the potential positive and negative biological functions of such host proteins. The studies conducted herein utilized proteomic analysis to identify differences in the spectrum of host proteins acquired by a single source of SIV replicating within CD4+ T cells from disease resistant sooty mangabeys and disease susceptible rhesus macaques.

Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue.

Background: The human immunodeficiency virus type 1 (HIV-1) Vpu protein degrades CD4 and counteracts a restriction factor termed tetherin (CD317; Bst-2) to enhance virion release. It has been suggested that both functions can be genetically separated by mutation of a serine residue at position 52. However, recent data suggest that the S52 phosphorylation site is also important for the ability of Vpu to counteract tetherin.