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Bentley S.D.,Wellcome Trust Sanger Institute | Comas I.,Genomics and Health Unit | Comas I.,UK National Institute for Medical Research | Bryant J.M.,Wellcome Trust Sanger Institute | And 17 more authors.
PLoS Neglected Tropical Diseases | Year: 2012

Background: M. africanum West African 2 constitutes an ancient lineage of the M. tuberculosis complex that commonly causes human tuberculosis in West Africa and has an attenuated phenotype relative to M. tuberculosis. Methodology/Principal Findings: In search of candidate genes underlying these differences, the genome of M. africanum West African 2 was sequenced using classical capillary sequencing techniques. Our findings reveal a unique sequence, RD900, that was independently lost during the evolution of two important lineages within the complex: the "modern" M. tuberculosis group and the lineage leading to M. bovis. Closely related to M. bovis and other animal strains within the M. tuberculosis complex, M. africanum West African 2 shares an abundance of pseudogenes with M. bovis but also with M. africanum West African clade 1. Comparison with other strains of the M. tuberculosis complex revealed pseudogenes events in all the known lineages pointing toward ongoing genome erosion likely due to increased genetic drift and relaxed selection linked to serial transmission-bottlenecks and an intracellular lifestyle. Conclusions/Significance: The genomic differences identified between M. africanum West African 2 and the other strains of the Mycobacterium tuberculosis complex may explain its attenuated phenotype, and pave the way for targeted experiments to elucidate the phenotypic characteristic of M. africanum. Moreover, availability of the whole genome data allows for verification of conservation of targets used for the next generation of diagnostics and vaccines, in order to ensure similar efficacy in West Africa. © 2012 Bentley et al.


Hamza E.,University of Bern | Gerber V.,University of Bern | Steinbach F.,Veterinary Laboratories Agency VLA | Marti E.,University of Bern
Immunology | Year: 2011

Horses are particularly prone to allergic and autoimmune diseases, but little information about equine regulatory T cells (Treg) is currently available. The aim of this study therefore was to investigate the existence of CD4 + Treg cells in horses, determine their suppressive function as well as their mechanism of action. Freshly isolated peripheral blood mononuclear cells (PBMC) from healthy horses were examined for CD4, CD25 and forkhead box P3 (FoxP3) expression. We show that equine FoxP3 is expressed constitutively by a population of CD4 +CD25 + T cells, mainly in the CD4 +CD25 high subpopulation. Proliferation of CD4 +CD25 - sorted cells stimulated with irradiated allogenic PBMC was significantly suppressed in co-culture with CD4 +CD25 high sorted cells in a dose-dependent manner. The mechanism of suppression by the CD4 +CD25 high cell population is mediated by close contact as well as interleukin (IL)-10 and transforming growth factor-β1 (TGF-β1) and probably other factors. In addition, we studied the in vitro induction of CD4 + Treg and their characteristics compared to those of freshly isolated CD4 + Treg cells. Upon stimulation with a combination of concanavalin A, TGF-β1 and IL-2, CD4 +CD25 + T cells which express FoxP3 and have suppressive capability were induced from CD4 +CD25 - cells. The induced CD4 +CD25 high express higher levels of IL-10 and TGF-β1 mRNA compared to the freshly isolated ones. Thus, in horses as in man, the circulating CD4 +CD25 high subpopulation contains natural Treg cells and functional Treg can be induced in vitro upon appropriate stimulation. Our study provides the first evidence of the regulatory function of CD4 +CD25 + cells in horses and offers insights into ex vivo manipulation of Treg cells. © 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd.


Alban L.,Danish Agriculture and Food Council DAFC | Pozio E.,Istituto Superiore di Sanita | Boes J.,Danish Agriculture and Food Council DAFC | Boireau P.,Agence Francaise de Securite Sanitaire des Aliments AFSSA | And 17 more authors.
Preventive Veterinary Medicine | Year: 2011

Each year, more than 167 million pigs in the European Union (EU) are tested for Trichinella spp. under the current meat hygiene regulations. This imposes large economic costs on countries, yet the vast majority of these pigs test negative and the public health risk in many countries is therefore considered very low. This work reviewed the current Trichinella status across the EU as well as the national level of monitoring and reporting. It also reviewed which animal species were affected by Trichinella and in which species it should be surveyed. This information was used to design a cost-effective surveillance programme that enables a standardised monitoring approach within the EU. The proposed surveillance programme relies on identifying sub-populations of animals with a distinct risk. Low-risk pigs are finisher pigs that originate from so-called controlled housing. All other pigs are considered high-risk pigs. Controlled housing is identified by the application of a specific list of management and husbandry practices. We suggest that member states (MS) be categorised into three classes based on the confidence that Trichinella can be considered absent, in the specified sub-population of pigs above a specified design prevalence which we set to 1 per million pigs. A simple and transparent method is proposed to estimate this confidence, based on the sensitivity of the surveillance system, taking into account the sensitivity of testing and the design prevalence. The probability of detecting a positive case, if present, must be high (>95 or >99%) to ensure that there is a low or negligible risk of transmission to humans through the food chain. In MS where the probability of a positive pig is demonstrated to be negligible, testing of fattening pigs from a sub-population consisting of pigs from controlled housing can be considered unnecessary. Furthermore, reduced testing of finishers from the sub-population consisting of pigs from non-controlled housing might even be considered, if conducted in conjunction with a proportionate sampling scheme and a risk-based wildlife surveillance programme where applicable. The proposed surveillance programme specifies the required number of samples to be taken and found negative, in a MS. A MS with no data or positive findings will initially be allocated to class 1, in which all pigs should be tested. When a MS is able to demonstrate a 95% or 99% confidence that Trichinella is absent, the MS will be allocated to class 2 or 3, in which the testing requirement is lower than in class 1. © 2011 Elsevier B.V.


Akhvlediani T.,Georgia Institute of Technology | Chitadze N.,National Center for Disease Control and Public Health | Laws T.R.,UK Defence Science and Technology Laboratory | Makharadze M.,Institute of Tropical Medicine | And 12 more authors.
Journal of Infection and Public Health | Year: 2012

Brucellosis is an ancient disease that still remains a significant threat to humans and is typically linked to exposure to infected animals and/or consumption of unpasteurized animal products. Despite this history, we have a relatively limited understanding of the host characteristics of this disease; consequently, further research is necessary. In this study, we examined the humoral immune response in 43 Georgian individuals that had been diagnosed with brucellosis 3-12. months before enrollment in the study, many of whom still had symptoms after the completion of antibiotic therapy. In total, 35 of 43 (83%) of the patients had antibodies that bound to Brucella lipopolysaccharide (LPS) by COMPELISA, and 34 of 38 (89%) patients had demonstrable specific antibodies to Brucellergene™ antigens; the results from the two ELISAs were highly correlated (p= 0.031, r= 0.851). We also studied the cellular immune responses in 15 patients. All of the patients generated interferon (IFN)-γ in response to ex vivo stimulation with Brucella protein antigens, and the majority of the patients maintained measurable humoral responses to both LPS and protein antigens. From this initial study, we conclude that measurement of antibody and of cellular (IFN-γ) responses to brucellergene OCB protein epitopes may be worthy of further investigation as an alternative or adjunct to current diagnostics. © 2012 King Saud Bin Abdulaziz University for Health Sciences.


Searle L.E.J.,Veterinary Laboratories Agency VLA | Cooley W.A.,Veterinary Laboratories Agency VLA | Jones G.,Veterinary Laboratories Agency VLA | Nunez A.,Veterinary Laboratories Agency VLA | And 8 more authors.
Journal of Medical Microbiology | Year: 2010

The prebiotic Bimuno® is a mixture containing galactooligosaccharides (GOSs), produced by the galactosyltransferase activity of Bifidobacterium bifidum NCIMB 41171 using lactose as the substrate. Previous in vivo and in vitro studies demonstrating the efficacy of Bimuno® in reducing Salmonella enterica serovar Typhimurium (S. Typhimurium) colonization did not ascertain whether or not the protective effects could be attributed to the prebiotic component GOS. Here we wished to test the hypothesis that GOS, derived from Bimuno®, may confer the direct anti-invasive and protective effects of Bimuno®. In this study the efficacy of Bimuno®, a basal solution of Bimuno® without GOS [which contained glucose, galactose, lactose, maltodextrin and gum arabic in the same relative proportions (w/w) as they are found in Bimuno®] and purified GOS to reduce S. Typhimurium adhesion and invasion was assessed using a series of in vitro and in vivo models. The novel use of three dimensionally cultured HT-29-16E cells to study prebiotics in vitro demonstrated that the presence of ∼5 mg Bimuno® ml-1 or ∼2.5 mg GOS ml-1 significantly reduced the invasion of S. Typhimurium (SL1344nalr) (P<0.0001). Furthermore, ∼2.5 mgGOS ml-1 significantly reduced the adherence of S. Typhimurium (SL1344nalr) (P<0.0001). It was demonstrated that cells produced using this system formed multi-layered aggregates of cells that displayed excellent formation of brush borders and tight junctions. In the murine ligated ileal gut loops, the presence of Bimuno® or GOS prevented the adherence or invasion of S. Typhimurium to enterocytes, and thus reduced its associated pathology. This protection appeared to correlate with significant reductions in the neutral and acidic mucins detected in goblet cells, possibly as a consequence of stimulating the cells to secrete the mucin into the lumen. In all assays, Bimuno® without GOS conferred no such protection, indicating that the basal solution confers no protective effects against S. Typhimurium. Collectively, the studies presented here clearly indicate that the protective effects conferred by Bimuno® can be attributed to GOS. © 2010 Crown copyright.

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