Molecular correlates of vaccine-induced protection against typhoid fever
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE217667 | GEO | 2023/07/19
REPOSITORIES: GEO
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Project description:We were able to obtain distinct gene expression profile between children with typhoid fever and other bacteremic infections. Peripheral blood of Nigerian children with typhoid fever and other bacteremic infection were obtained in Paxgene tubes. Total RNa were extracted using Paxgene blood RNA kit and 4x44K (G4112F) human GE array were processed according to standard Agilent procedures
2011-11-29 | E-GEOD-28658 | biostudies-arrayexpress
Project description:We were able to obtain distinct gene expression profile between children with typhoid fever and other bacteremic infections.
2011-11-29 | GSE28658 | GEO
Project description:Enteric fever is a major public health problem and causes numerous deaths annually. Ty21a is the only efficacious oral, live attenuated typhoid vaccine currently licensed for use, however, its mechanism of protection is poorly understood. To address this knowledge gap, we interrogated transcriptional profiles following vaccination with Ty21a and an immunogenic experimental oral live attenuated vaccine, M01ZH09, and related these findings to immunogenicity, and incubation period and disease severity following challenge with Salmonella Typhi four weeks after vaccination. Despite originating from the same parent strain (Ty2), we detected marked differences in the gene expression between both vaccines. Analysis of the transcriptome 7 days after M01ZH09 vaccination implicated transcriptional patterns associated with the cell cycle correlated significantly with humoral immunogenicity 28 days after vaccination. In contrast, significantly induced T and NK cell responses were associated with Ty21a vaccination, and integrative analysis indicated signatures reflecting amino acid metabolism with delayed onset of disease. Stimulation of PBMCs collected from participants prior to and following vaccination with the two vaccine strains in vitro confirmed the superior capacity of Ty21a to induce NK cells, validating gene expression results. These data provide insight into the effects of oral live attenuated typhoid vaccines on the human molecular immune response and underline the involvement of T cell response signatures with protection following challenge.
2017-10-12 | GSE100665 | GEO
Project description:Salmonella enterica serovar Typhi (S. Typhi), a human-restricted pathogen, enters the host through the gut to cause typhoid fever. Recent calculations of the typhoid fever burden estimated that more than 20 million new typhoid fever cases occur in low and middle-income countries, resulting in 129,000-223,000 deaths yearly. Interestingly, upon the resolution of acute disease, 1%-5% of patients become asymptomatic chronic carriers of S. Typhi. Chronically infected hosts are not only critical reservoirs of infection that transmit the disease to naive individuals but are also predisposed to developing gallbladder carcinoma (GBC). Nevertheless, the molecular mechanisms involved in the early interactions between gallbladder epithelial cells and S. Typhi remain largely unknown. Based on our previous studies showing that very closely related S. Typhi strains elicit distinct innate immune responses, we hypothesized that host molecular pathways activated by S. Typhi strains derived from acutely and chronically infected patients will differ. To test this hypothesis, we used a novel human organoid-derived polarized gallbladder monolayer (HODGM) model, and 13 S. Typhi strains derived from acutely (n=6) and chronically (n=7) infected patients. We found that S. Typhi strains derived from acutely and chronically infected patients differentially regulate mitogen-activated protein kinase (MAPK) and S6 transcription factors. This differential regulation impacts, at least in part, the cytokine signaling pathway involved in the production of TNF- and IL-6 and is likely to play a critical role in inducing chronic S. Typhi infection in the gallbladder.
2024-04-05 | GSE253700 | GEO
Project description:Patient Selection: Three hospitals were involved in the study: Dong Thap Provincial and An Giang Provincial hospitals, both located in the Mekong Delta Region of Vietnam where most of the Typhoid patients were admitted, and the Hospital for Tropical Diseases, Ho Chi Minh City, where the malarial patients were admitted. Infection status of each patient was determined by blood culture for the Typhoid patients and by microscopic examination of stained thick and thin peripheral-blood slides for the patients suspected of having Malaria. Patients with blood cultures positive for S. Typhi or S. enterica serovar Paratyphi A (S. Paratyphi A) (samples designated ST) or peripheral blood smears positive for Plasmodium falciparum or Plasmodium vivax (samples designated PF) were consented and enrolled in the study. A total of 28 S. Typhi positive patients and one S. Paratyphi A positive patient were enrolled in the first phase of the study and a further 9 S. Typhi and one S. Paratyphi A positive patient were enrolled in the second phase. Nine patients with Malaria caused by P. falciparum and one caused by P. vivax were enrolled. Sixteen uninfected healthy individuals (samples designated HC) were also enrolled in the study (one sample each). The Typhoid patients were randomly chosen to receive either Azithromycin or Gatifloxicin (20mg/kg/day for 7 days) antibiotics. Uncomplicated malaria patients were treated for 3 days with Artekin (dihydroartemisinin with piperaquine phosphate). Venous blood (2.5ml) was collected for total RNA extraction into PaxGene RNA collection tubes (Qiagen) at various times. The first sample (T1) was taken immediately on admission or entry into the study, then samples were collected, 3 (T3), 6-9 (T9 for Typhoid, T7 for Malaria), and 28-45 (T28) days following entry into the study and an average of 9 months (T9M) later. The PaxGene tubes were stored at 4degC until RNA was extracted as per the manufacturers instructions. Purified RNA was shipped on dry ice to Stanford University, CA for use in Microarray analyses. Microarrays: Experimental and reference samples (Human Universal RNA reference {Stratagene}) were amplified using the MessageAmp II aRNA Kit (Ambion) as per the manufacturer's instructions. Four micrograms amplified RNA was labeled through indirect incorporation of Cy5 (experimental) and Cy3 (reference) dyes (protocols can be found at http://cmgm.stanford.edu/pbrown/protocols/index.html). The labeled probes were then mixed and hybridized to Stanford Human cDNA arrays with 42 K features. Arrays were scanned using a Genepix 4000A laser scanner and data extracted with Genepix Pro Software version 5.1 (Axon Instruments). The data were then uploaded into the Stanford Microarray Database (SMD). A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Compound Based Treatment: Drugs used for treatment Disease State: Malaria, Typhoid or Healthy Controls Keywords: disease_state_design Complex
2010-01-03 | E-GEOD-7000 | biostudies-arrayexpress
Project description:Patient Selection: Three hospitals were involved in the study: Dong Thap Provincial and An Giang Provincial hospitals, both located in the Mekong Delta Region of Vietnam where most of the Typhoid patients were admitted, and the Hospital for Tropical Diseases, Ho Chi Minh City, where the malarial patients were admitted. Infection status of each patient was determined by blood culture for the Typhoid patients and by microscopic examination of stained thick and thin peripheral-blood slides for the patients suspected of having Malaria. Patients with blood cultures positive for S. Typhi or S. enterica serovar Paratyphi A (S. Paratyphi A) (samples designated ST) or peripheral blood smears positive for Plasmodium falciparum or Plasmodium vivax (samples designated PF) were consented and enrolled in the study. A total of 28 S. Typhi positive patients and one S. Paratyphi A positive patient were enrolled in the first phase of the study and a further 9 S. Typhi and one S. Paratyphi A positive patient were enrolled in the second phase. Nine patients with Malaria caused by P. falciparum and one caused by P. vivax were enrolled. Sixteen uninfected healthy individuals (samples designated HC) were also enrolled in the study (one sample each). The Typhoid patients were randomly chosen to receive either Azithromycin or Gatifloxicin (20mg/kg/day for 7 days) antibiotics. Uncomplicated malaria patients were treated for 3 days with Artekin (dihydroartemisinin with piperaquine phosphate). Venous blood (2.5ml) was collected for total RNA extraction into PaxGene RNA collection tubes (Qiagen) at various times. The first sample (T1) was taken immediately on admission or entry into the study, then samples were collected, 3 (T3), 6-9 (T9 for Typhoid, T7 for Malaria), and 28-45 (T28) days following entry into the study and an average of 9 months (T9M) later. The PaxGene tubes were stored at 4degC until RNA was extracted as per the manufacturers instructions. Purified RNA was shipped on dry ice to Stanford University, CA for use in Microarray analyses. Microarrays: Experimental and reference samples (Human Universal RNA reference {Stratagene}) were amplified using the MessageAmp II aRNA Kit (Ambion) as per the manufacturer's instructions. Four micrograms amplified RNA was labeled through indirect incorporation of Cy5 (experimental) and Cy3 (reference) dyes (protocols can be found at http://cmgm.stanford.edu/pbrown/protocols/index.html). The labeled probes were then mixed and hybridized to Stanford Human cDNA arrays with 42 K features. Arrays were scanned using a Genepix 4000A laser scanner and data extracted with Genepix Pro Software version 5.1 (Axon Instruments). The data were then uploaded into the Stanford Microarray Database (SMD). A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Compound Based Treatment: Drugs used for treatment Disease State: Malaria, Typhoid or Healthy Controls Keywords: disease_state_design
2010-01-04 | GSE7000 | GEO
Project description:Human genetic diversity can reveal critical factors in host-pathogen interactions. This is especially useful for human-restricted pathogens like Salmonella enterica serovar Typhi (S. Typhi), the cause of Typhoid fever. One key dynamic during infection is competition for nutrients: host cells attempt to restrict intracellular replication by depriving bacteria of key nutrients or delivering toxic metabolites in a process called nutritional immunity. Here, a cellular genome-wide association study of intracellular replication by S. Typhi in nearly a thousand cell lines from around the world—and extensive follow-up using intracellular S. Typhi transcriptomics and manipulation of magnesium concentrations—demonstrates that the divalent cation channel mucolipin-2 (MCOLN2) restricts S. Typhi intracellular replication through magnesium deprivation. Our results reveal natural diversity in Mg2+ limitation as a key component of nutritional immunity against S. Typhi.
2023-01-05 | GSE222194 | GEO
Project description:Background: Salmonella Typhi and Salmonella Paratyphi A are the agents of enteric (typhoid) fever; both can establish chronic carriage in the gallbladder. Chronic Salmonella carriers are typically asymptomatic, intermittently shedding bacteria in the feces, and contributing to disease transmission. Detecting chronic carriers is of public health relevance in areas where enteric fever is endemic, but there are no routinely used methods for prospectively identifying those carrying Salmonella in their gallbladder. Methodology/Principal Findings: Here we aimed to identify biomarkers of Salmonella carriage using metabolite profiling. We performed metabolite profiling on plasma from Nepali patients undergoing cholecystectomy with confirmed S. Typhi or S. Paratyphi A gallbladder carriage (and non-carriage controls) using two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS) and supervised pattern recognition modeling. We were able to significantly discriminate Salmonella carriage samples from non-carriage control samples. We were also able to detect differential signatures between S. Typhi and S. Paratyphi A carriers. We additionally compared carriage metabolite profiles with profiles generated during acute infection; these data revealed substantial heterogeneity between metabolites associated with acute enteric fever and chronic carriage. Lastly, we found that Salmonella carriers could be significantly distinguished from non-carriage controls using only five metabolites, indicating the potential of these metabolites as diagnostic markers for detecting chronic Salmonella carriers. Conclusions/Significance: Our novel approach has highlighted the potential of using metabolomics to search for diagnostic markers of chronic Salmonella carriage. We suggest further epidemiological investigations of these potential biomarkers in alternative endemic enteric fever settings.
2018-01-17 | MTBLS579 | MetaboLights
Project description:This study describes how Salmonella Typhi, the pathogen responsible for typhoid fever, uses similar strategies to escape immune defense responses and survive within its human host. To elucidate the early mechanisms of typhoid fever, we performed studies using healthy human intestinal tissue samples to analyze gene expression changes in human intestinal specimens and bacterial cells both separately and after colonization. Our results showed mechanistic strategies that S. Typhi uses to rearrange the cellular machinery of the host cytoskeleton to successfully invade the intestinal epithelium, promote polarized cytokine release and evade immune system activation by downregulating genes involved in antigen sampling and presentation during infection.
2018-06-15 | GSE113333 | GEO
Project description:Infection with Salmonella enterica serovar Typhi in humans causes the systemic, life-threatening disease typhoid fever. In the laboratory, typhoid fever can be modeled through the inoculation of susceptible mice with Salmonella enterica serovar Typhimurium. The ensuing disease is characterized by systemic dissemination and colonization of many organs, including the liver, spleen and gallbladder. Using this murine model, we previously characterized the interactions between Salmonella Typhimurium and host cells in the gallbladder and showed that this pathogen can successfully invade gallbladder epithelial cells and proliferate. Additionally, we showed that Salmonella Typhimurium can use bile phospholipids to grow at high rates. These abilities are likely important for quick colonization of the gallbladder during typhoid fever and further pathogen dissemination through fecal shedding. To further characterize the interactions between Salmonella and the gallbladder environment we compared the transcriptome of Salmonella cultures grown in LB or physiological murine bile. Our data showed that many genes involved in bacterial central metabolism are affected by bile, with the citric acid cycle being repressed and alternative respiratory systems being activated. Additionally, our study revealed a new aspect of Salmonella interactions with bile through the identification of phoP as a bile-responsive gene. Repression of phoP expression does not involve PhoPQ sensing of a bile component. Due to its critical role in Salmonella virulence, further studies in this area will likely reveal aspects of the interaction between Salmonella and bile that are relevant to disease.
2011-11-10 | GSE33604 | GEO