Genes Influencing Susceptibility to Infection and Malnutrition
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PROVIDER: PRJNA416029 | ENA |
REPOSITORIES: ENA
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Project description:Genes Influencing Susceptibility to Infection and Malnutrition
| PRJNA416030 | ENA
Project description:<p><b>NIH birth cohort study</b><br/> Amebiasis is a common cause of diarrhea and is associated with malnutrition in grade-school aged children in an urban slum of Dhaka, Bangladesh. Field Studies of Human Immunity to Amebiasis in Bangladesh was designed to determine the contribution of amebiasis to illness in the first 2 years of life when most deaths due to diarrhea occur, and understand the immunologic and genetic factors that protect children from amebiasis.</p> <p>The hypothesis underlying the study is that susceptibility to amebiasis is determined by host innate and acquired immune responses that vary between individuals in part due to: human genetic polymorphisms; environmental influences including malnutrition and concurrent geohelminth infection; and virulence differences among Entamoeba histolytica genotypes.</p> <p>Specific aims proposed in the design of the study were to:<br/> a) Measure the incidence of amebiasis and correlate it with human and parasite genetic polymorphisms, immune responses, and environmental factors such as geohelminth infection and malnutrition;<br/> b) Test the hypothesis that protective immunity is mediated both by innate immune responses initiated via TLR stimulation as well as by mucosal IgA against the Gal/GalNAc lectin and systemic IFN-γ;<br/> c) Test for the association of common genetic polymorphisms in host innate and acquired immune genes with incidence of amebiasis. </p> <p>629 newborn babies were enrolled and followed regularly through bi-weekly surveillance for diarrheal episodes, anthropometry at 3-month interval until 60 months of age.</p> <p>The infants that were consented for GWAS analysis were genotyped in 3 separate batches at different times, on 3 different arrays. Quality control was performed on the 3 separate data sets and then jointly after merging.</p> <p>Genetic data available on 447 infants together with their phenotype data is made available in this submission</p> <p><b>PROVIDE</b> (<b>P</b>erformance of <b>R</b>otavirus and <b>O</b>ral <b>P</b>olio <b>V</b>accines <b>i</b>n <b>De</b>veloping Countries) <b>Study</b><br/> Oral polio and rotavirus vaccines are significantly less effective in children living in the developing world. Environmental enteropathy, which is associated with intestinal inflammation, decreased absorption and increased permeability, may contribute substantially to oral vaccine failure in developing country settings. The primary objective of the study was to determine the association of environmental enteropathy with the efficacy of oral polio and rotavirus vaccines in children in Bangladesh. Secondary and exploratory objectives were designed to address other possible causes of oral vaccine underperformance including malnutrition, interference with maternal or breastmilk antibodies, changes in gut microbiota, and genetic susceptibility. </p> <p>The PROVIDE study was structured as a 2x2 clinical trial with a prospective birth cohort enrollment of 700 infants and their mothers in the urban slum of Mirpur, Dhaka, Bangladesh. All children received the full series of Bangladesh's Expanded Program on Immunization vaccines, including oral polio vaccine (OPV) and followed for their first 2 years of life. Half the children were randomized to receive an inactivated polio vaccine (IPV) for their 4th dose at 39 weeks instead of the standard OPV dose. In the other trial, half the infants received the 2-dose rotavirus vaccine (Rotarix) with delayed dosing at 10 and 17 weeks of age.</p> <p>A detailed description of the study design and procedures can be obtained from PROVIDE methods publication: Kirkpatrick B.D., Colgate R.E., Mychaleckyj J.C., Haque R., Dorothy D.M., Carmolli M.P., et al. (2015) Am J Trop Med Hyg 92, 744-751</p> <p>The Poliovirus trial and results are described in Mychaleckyj et al, Vaccine 2016</p> <p>The Rotavirus trial and results are described in Colgate et al, Clin Infect Dis 2016</p> <p>The PROVIDE infants were genotyped on a custom Affymetrix Axiom array (30K SNPs) at the University of Virginia Center for Public Health Genomics; and on a pre-production version of the Illumina MEGA v2 chip at the Wellcome Trust Sanger Institute, UK. The latter genotyping was performed under the auspices of the VaccGene Consortium. Analyses are ongoing to identify variants associated with the included phenotypes. A manuscript describing the genotyping methods and analysis is in preparation for the initial phenotypes.</p> <p><b>The Infection Malnutrition Bangladesh Cohort is utilized in the following dbGaP sub-studies.</b> To view genotypes, other molecular data, and derived variables collected in these sub-studies, please click on the following sub-studies below or in the "Sub-studies" box located on the right hand side of this top-level study page <a href="study.cgi?study_id=phs001475">phs001475</a> Infection Malnutrition Bangladesh Cohort. <ul> <li><a href="study.cgi?study_id=phs001476">phs001476</a> Amebiasis Immunity</li> <li><a href="study.cgi?study_id=phs001478">phs001478</a> Polio Rotavirus Vaccines</li> <li><a href="study.cgi?study_id=phs001665">phs001665</a> Cryptosporidiosis Enteropathogens</li> </ul> </p>
| phs001475 | dbGaP
Project description:The thymus is one of the most affected organs during malnutrition, exhibiting atrophy and thymocyte depletion, characteristics that are also observed in several infectious diseases. The detrimental effects of malnutrition on immune responses to pathogens have long been recognized and it is considered a main risk factor for various infectious diseases, including visceral leishmaniasis (VL). However, the thymus has been barely studied during malnutrition and Leishmania infantum infection association. Protein malnutrition modifies intrathymic communication in L. infantum infected BALB/c mice by altering the abundance of proteins secreted to the thymic interstitial fluid (IF). We identified and compared protein abundance in the thymic IF samples from BALB/c mice that were fed with control protein (14%, CP) or low protein (4%, LP) isocaloric diets, followed by infection with L. infantum. By means of a quantitative proteomics approach using iTRAQ we identified 280 proteins of which 81% were reported as secreted by exosomes and 42% were previously described as secreted by thymic epithelial cells. LP-infected (LPi) animals showed a significant decrease in exosomal proteins, suggesting that exosomal carrier system is dysregulated in malnourished animals. LPi mice also exhibited an increase in the relative abundance of proteins involved in lipid metabolism and tricarboxylic acid cycle, suggestive of a non-proliferative microenvironment. Accordingly, flow cytometry analysis revealed that protein malnutrition decreases the proliferation of single positive and double positive T cells. Proteins engaged in glycolysis, protein ubiquitination and mRNA processing were significantly decreased. In addition, a significant decrease in the abundance of galectin-1 and increase of plasminogen were observed in malnourished animals. Together, the reduced cortical area, decreased proliferation, increased abundance of lipid- and tricarboxylic acid cycle-related proteins, and altered abundance of galectin-1 and plasminogen indicate a dysfunctional thymic microenvironment, where T cell migration, proliferation and maturation are compromised, contributing for the thymic atrophy observed in malnourished animals. All these alterations affect the control of the local and systemic infection, resulting in an impaired response to L. infantum infection.
2019-11-12 | PXD010414 | Pride
Project description:It has been shown that inbred strains of mice exhibit variable susceptibility to S. aureus infection, but the specific genes responsible for this differential phenotype are unknown. Using ISHM to identify genomic regions associated with the phenotypes, we considered genes within those interval to be candidate genes and used the gene expression patterns of the genes contained in the region to determine whether the genes are differentially expressed between the 2 phenotypically different groups of mice. To identify genes differentially expressed between mice susceptible and resistant to S. aureus infection that could contribute to host susceptibility to S. aureus infection, we compared the gene expression profiles between 2 groups of mice where 3 were susceptible (A/J, BALBcBy/J, AKR/J) and resistant (C57BL/J, C3H/HeJ, NOD/ShiLtJ) to S. aureus. The susceptible group had high bacterial count values in the kidney while the resistant group had low values.
2011-12-31 | E-GEOD-23584 | biostudies-arrayexpress
Project description:It has been shown that inbred strains of mice exhibit variable susceptibility to S. aureus infection, but the specific genes responsible for this differential phenotype are unknown. Using ISHM to identify genomic regions associated with the phenotypes, we considered genes within those interval to be candidate genes and used the gene expression patterns of the genes contained in the region to determine whether the genes are differentially expressed between the 2 phenotypically different groups of mice.
2011-12-31 | GSE23584 | GEO
Project description:Microbes Malnutrition Microglia
| PRJNA575001 | ENA
Project description:Pulmonary infection induces scarred lipidome influencing response to unrelated challenge
| PRJNA719826 | ENA
Project description:Epigenetic Analysis of Malnutrition
| PRJNA312717 | ENA
Project description:Muscle cells are potential targets of many arboviruses, such as Ross River, Dengue, Sindbis, and Chikungunya viruses, that may be involved in the physiopathological course of the infection. During the recent outbreak of Zika virus (ZIKV), myalgia was one of the most frequently reported symptoms. We investigated the susceptibility of human muscle cells to ZIKV infection. Using an in vitro model of human primary myoblasts that can be differentiated into myotubes, we found that myoblasts can be productively infected by ZIKV. In contrast, myotubes were shown to be resistant to ZIKV infection, suggesting a differentiation-dependent susceptibility. Infection was accompanied by a caspase-independent cytopathic effect, associated with paraptosis-like cytoplasmic vacuolization. Proteomic profiling was performed 24h and 48h post-infection in cells infected with two different isolates. Proteome changes indicate that ZIKV infection induces an upregulation of proteins involved in the activation of the Interferon type I pathway, and a downregulation of protein synthesis. This work constitutes the first observation of primary human muscle cells susceptibility to ZIKV infection, and differentiation-dependent restriction of infection from myoblasts to myotubes. Since myoblasts constitute the reservoir of stem cells involved in reparation/regeneration in muscle tissue, the infection of muscle cells and the viral-induced alterations observed here could have consequences in ZIKV infection pathogenesis.
2020-05-11 | PXD017261 | Pride
Project description:GENOME-WIDE ANALYSIS FOR ADDICTION SUSCEPTIBILITY GENES
| PRJNA360500 | ENA