Publications by authors named "Silbart L"

Introduction: The commensal bacterium is a prominent member of the microbiome of animals and humans, and it plays an important role in several physiological processes. Numerous studies have correlated the reduction of abundance with many disease states, including irritable bowel syndrome, Crohn's disease, obesity, asthma, major depressive disorder, and metabolic diseases in humans. Studies have also correlated with diseases in humans involved in altered glucose metabolism, including diabetes.

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Development of an effective vaccine for Mycoplasma pneumoniae has been hindered by reports of Vaccine Enhanced Disease (VED) in test subjects vaccinated and challenged in studies conducted in the 1960s. The exact mechanism of disease exacerbation has yet to be fully described, but host immune responses to Lipid-Associated Membrane Proteins (LAMPs) lipoprotein lipid moieties have been implicated. LAMPs-induced exacerbation appears to involve helper T cell recall responses, due in part to their influence on neutrophil recruitment and subsequent inflammatory responses in the lung.

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Article Synopsis
  • Bacterial lipoproteins can cause strong immune reactions but are often overlooked in vaccine development.
  • Vaccinating mice with Mycoplasma pneumoniae lipoproteins led to an immune response that unexpectedly worsened the disease after exposure to the virus.
  • Increased levels of inflammatory cytokines and neutrophils were observed in the lungs, indicating that IL-17A plays a crucial role in this maladaptive immune response, while neutrophils contributed negatively to the disease's severity.
  • The research highlights the need to consider potential negative immune responses when designing vaccines targeting bacterial infections.
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Article Synopsis
  • - Scientists discovered a new T cell co-inhibitory molecule called TAPBPL, which is similar to existing B7-family proteins and is found on various immune cells and some tumors.
  • - The study shows that a recombinant version of TAPBPL can inhibit T cell activity in lab settings and reduce symptoms of an autoimmune disease in mice when administered in vivo.
  • - Additionally, blocking TAPBPL with a specific antibody improves anti-tumor immunity and slows down tumor growth, suggesting that targeting this pathway could have potential for treating cancer and other immune-related conditions.
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Foot and Mouth Disease is a highly contagious and economically important disease of livestock. While vaccination is often effective at controlling viral spread, failures can occur due to strain mismatch or viral mutation. Foot and Mouth Disease Virus (FMDV) possesses a hypervariable region within the G-H Loop of VP1, a capsid protein commonly associated with virus neutralization.

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Background/aim: Previous work in rodent models showed that an autologous tissue vaccine is both a safe and effective approach for treating cancer; however, as a translational step, safety must first be evaluated in a more clinically-relevant model.

Materials And Methods: An autologous immunotherapy produced from resected tumors, was evaluated in a clinically-relevant canine model to assess safety. Ninety-three dogs with spontaneously occurring tumors received vaccination with inactivated autologous tumor tissue combined with an adjuvant of particulate porcine small intestinal submucosa extracellular matrix (SIS-ECM).

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Mycoplasmas are small bacterial commensals or pathogens that commonly colonize host mucosal tissues and avoid rapid clearance, in part by stimulating inflammatory, immunopathogenic responses. We previously characterized a wide array of transcriptomic perturbations in avian host tracheal mucosae infected with virulent, immunopathologic ; however, mechanisms delineating these from protective responses, such as those induced upon vaccination, have not been thoroughly explored. In this study, host transcriptomic responses to two experimental vaccines were assessed during the first 2 days of infection.

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, the primary etiologic agent of chronic respiratory disease (CRD) in poultry, leads to prolonged recruitment and activation of inflammatory cells in the respiratory mucosa. This is consistent with the current model of immune dysregulation that ostensibly allows the organism to evade clearance mechanisms and establish chronic infection. To date, studies using quantitative reverse transcription-PCR (qRT-PCR) and microarrays have shown a significant transient upregulation of cytokines and chemokines from tracheal epithelial cells (TECs) and tracheal tissue in response to virulent strain R that contributes to the infiltration of inflammatory cells into the tracheal mucosa.

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Mycoplasma gallisepticum colonizes the chicken respiratory mucosa and mediates a severe inflammatory response hallmarked by subepithelial leukocyte infiltration. We recently reported that the interaction of M. gallisepticum with chicken tracheal epithelial cells (TECs) mediated the upregulation of chemokine and inflammatory cytokine genes in these cells (S.

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Mycoplasma gallisepticum-mediated respiratory inflammation in chickens is associated with accumulation of leukocytes in the tracheal submucosa. However the molecular mechanisms underpinning these changes have not been well described. We hypothesized that the initial inflammatory events are initiated upon ligation of mycoplasma lipid associated membrane proteins (LAMP) to TLRs expressed on chicken tracheal epithelial cells (TEC).

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The incidence of atopic conditions has increased in industrialized countries. Persisting symptoms and concern for drug side-effects lead patients toward adjunctive treatments such as phytotherapy. Previously, we have shown that Bromelain (sBr), a mixture of cysteine proteases from pineapple, Ananas comosus, inhibits ovalbumin (OVA)-induced murine model of allergic airway disease (AAD).

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The migration of eosinophils and lymphocytes into airways is a hallmark of allergic asthma; however, the role of broncho-alveolar macrophages (BAMs) in this inflammatory process has not been fully elucidated. Using a murine Ova model of allergic airway disease (AAD), RNA isolated from BAMs was used to assess differential gene expression via microarray and qRT-PCR. Significant increases in WBCs, eosinophilia, mucus accumulation and goblet cell hyperplasia were observed in Ova sensitized and challenged mice, which correlated with increased expression of genes associated with alternatively activated M2 macrophages (e.

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Smokeless tobacco products have been associated with increased risks of oro-pharyngeal cancers, due in part to the presence of tobacco-specific nitrosamines (TSNAs) such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These potent carcinogens are formed during tobacco curing and as a result of direct nitrosation reactions that occur in the oral cavity. In the current work we describe the isolation and characterization of a hybridoma secreting a high-affinity, NNK-specific monoclonal antibody.

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Foot-and-mouth disease virus (FMDV) is a highly contagious pathogen that causes severe morbidity and economic losses to the livestock industry in many countries. The oral and respiratory mucosae are the main ports of entry of FMDV, so the stimulation of local immunity in these tissues may help prevent initial infection and viral spread. E.

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Bromelain (Br) is a cysteine peptidase (GenBank AEH26024.1) from pineapple, with over 40 years of clinical use. The constituents mediating its anti-inflammatory activity are not thoroughly characterized and no peptide biomarker exists.

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Many RNA viruses encode error-prone polymerases which introduce mutations into B and T cell epitopes, providing a mechanism for immunological escape. When regions of hypervariability are found within immunodominant epitopes with no known function, they are referred to as "decoy epitopes," which often deceptively imprint the host's immune response. In this work, a decoy epitope was identified in the foot-and-mouth disease virus (FMDV) serotype O VP1 G-H loop after multiple sequence alignment of 118 isolates.

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Peptides corresponding to the foot-and-mouth disease virus VP1 G-H loop are capable of inducing neutralizing antibodies in some species but are considered relatively poor immunogens, especially at mucosal surfaces. However, intranasal administration of antigens along with the appropriate delivery vehicle/adjuvant has been shown to induce mucosal immune responses, and bacterial enterotoxins have long been known to be effective in this regard. In the current study, two different carrier/adjuvant approaches were used to augment mucosal immunity to the FMDV O(1) BFS G-H loop epitope, in which the G-H loop was genetically coupled to the E.

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Mycoplasma pneumoniae is a significant human respiratory pathogen that causes high morbidity worldwide. No vaccine to prevent M. pneumoniae infection currently exists, since the mechanisms of pathogenesis are poorly understood.

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Grating-coupled surface plasmon resonance imaging (GCSPRI) utilizes an optical diffraction grating embossed on a gold-coated sensor chip to couple collimated incident light into surface plasmons. The angle at which this coupling occurs is sensitive to the capture of analyte at the chip surface. This approach permits the use of disposable biosensor chips that can be mass-produced at low cost and spotted in microarray format to greatly increase multiplexing capabilities.

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In order to augment responses to respiratory vaccines in swine, various adjuvants were intranasally coadministered with a foot-and-mouth disease virus (FMDV) antigen to pigs. Detoxified Escherichia coli enterotoxins LTK63 and LTR72 enhanced antigen-specific mucosal and systemic immunity, demonstrating their efficacy as adjuvants for nonreplicating antigens upon intranasal immunization in swine.

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Cronobacter sakazakii is an emerging foodborne pathogen that causes severe meningitis and meningoencephalitis in neonates. Currently there is a dearth of information available on the virulence factors of C. sakazakii and the pathogenic mechanisms involved in its neonatal infections.

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The efficiency of nonviral vectors for gene delivery may be enhanced by understanding the key barriers that limit the translocation of the therapeutic DNA into the nucleus. One such barrier is the instability of DNA in the cytoplasm. In this work, we have developed a method to dual-label plasmid DNA to be utilized as a tool to elucidate DNA instability during its trafficking in the intracellular microenvironment.

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Background: Eosinophilic infiltration into the airways is frequently associated with allergic asthma; however, the role of antigen deposition in mediating this phenomenon has not been studied in detail.

Objective: Using a murine model of ovalbumin (OVA) allergy, we examined how differential deposition of OVA during antigen challenge affects pulmonary eosinophilia, immune response and airway hyper-reactivity (AHR).

Methods: Differential allergen deposition to the upper respiratory tract (URT) alone or combined upper and lower respiratory tract (ULRT) was accomplished by administering OVA intranasally to either anaesthetized or unanaesthetized mice, respectively.

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In a previous study, signature sequence mutagenesis (SSM) was used to identify a mutant with a disruption of the gene encoding the metabolic factor, dihydrolipoamide dehydrogenase, and that mutant was designated Mg 7. The current study assessed the safety, immunogenicity and efficacy of Mg 7 in comparison to two commercially available vaccines (ts-11 and F) as well as a laboratory vaccine strain, GT5. Intratracheal vaccination of chickens with all four attenuated mutants induced varying levels of protection against intratracheal challenge with virulent Mycoplasma gallisepticum strain R(low).

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Mycoplasma gallisepticum infection in chickens leads to tracheitis, airsacculitis, poor feed conversion and reduced egg production, resulting in considerable economic hardship on the poultry industry. The chemokines and cytokines responsible for recruitment, activation and proliferation of leukocytes in affected tissues have not been described. In the current study, chemokine and cytokine gene expression profiles were investigated in tracheas of chickens inoculated with M.

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