Project description:SARS-CoV-2 infection ranges from asymptomatic to severe with lingering symptomatology in some. This prompted investigation of whether or not asymptomatic disease results in measurable immune activation post-infection. Immune activation following asymptomatic SARS-CoV-2 infection was characterized through a comparative investigation of the immune cell transcriptomes from 43 asymptomatic seropositive and 52 highly exposed seronegative individuals from the same community four to six weeks following a superspreading event. Few of the 95 individuals had underlying health issues. One seropositive individual reported Cystic Fibrosis and one individual reported Incontinentia pigmenti. No evidence of immune activation was found in asymptomatic seropositive individuals with the exception of the Cystic Fibrosis patient. There were no statistically significant differences in immune transcriptomes between asymptomatic seropositive and highly exposed seronegative individuals. Four positive controls, mildly symptomatic seropositive individuals whose blood was examined three weeks following infection, showed immune activation. Negative controls were four seronegative individuals from neighboring communities without COVID19. All individuals remained in their usual state of health through a five-month follow-up after sample collection. In summary, whole blood transcriptomes identified individual immune profiles within a community population and showed that asymptomatic infection within a super-spreading event was not associated with enduring immunological activation.
Project description:Immune transcriptomes of highly exposed SARS-CoV-2 asymptomatic seropositive versus seronegative individuals from the Ischgl community
Project description:MicroRNAs have emerged as relevant players in resistance to infection. We aimed to identify miRNAs involved in natural resistance to dengue infection. Two groups of people living in dengue endemic area were classified as susceptible (SD) or resistant (RD) to dengue virus (DENV) infection according to their anti-DENV antibody status. We hypothesized that anti-DENV seronegative individuals may represent a population resistant to DENV infection. The miRNome from monocytes of 7 individuals of each group was assessed upon mock- or DENV-2 infection.Dysregulated miRNAs were chosen as candidates for functional studies.
Project description:We used Affymetix HG Focus GeneChip to measure the expression levels of HIV seronegative and seropositive individuals in human PBMCs in vivo. GSM39104 -GSM39115 are HIV seronegative samples; GSM39116-GSM39137 are HIV seropositive but drug naive samples; GSM39138-GSM39147 are HIV seropositive samples used to test serostatus biomarker; GSM39148-GSM39170 are HIV seropositive individuals whose CD4 cells decrease over time; GSM39171-GSM39187 are HIV seropositive individuals whose CD4 cells increase over time; GSM39188-GSM39190 are HIV seropositive samples used to test CD4 cell increase/decrease over time.
Project description:We used Affymetix HG Focus GeneChip to measure the expression levels of HIV seronegative and seropositive individuals in human PBMCs in vivo. GSM39104 -GSM39115 are HIV seronegative samples; GSM39116-GSM39137 are HIV seropositive but drug naive samples; GSM39138-GSM39147 are HIV seropositive samples used to test serostatus biomarker; GSM39148-GSM39170 are HIV seropositive individuals whose CD4 cells decrease over time; GSM39171-GSM39187 are HIV seropositive individuals whose CD4 cells increase over time; GSM39188-GSM39190 are HIV seropositive samples used to test CD4 cell increase/decrease over time. Keywords: other
Project description:Dengue represents one of the most serious life-threatening vector-borne infectious diseases that afflict ~50 million people across the globe annually. Whilst symptomatic infections are frequently reported, asymptomatic dengue largely remain unnoticed. The immune correlates conferring protection to individuals that remain clinically asymptomatic have seldom been investigated. We determined the gene expression profiles of host immune factors in individuals with asymptomatic infections, and whose cognate household members showed symptoms and signs consistent to clinical dengue infection. Results provide insight in association of certain host genes to protection against clinical dengue.
Project description:Caprine arthritis and encephalitis (CAE), caused by small ruminant lentivirus (SRLV), is a key disease of goats, with chronic inflammation of joints and brain symptoms, leading to losses in milk production and animal trade. In this study we analyzed gene expressions in milk somatic cells (MSCs) of seropositive (SRLV-SP) and seronegative (SRLV-SN) goats to identify transcriptomic changes using a non-invasive sampling method. Materials and Methods: The study was conducted on goats of two Polish breeds (Polish Improved White and Polish Improved Fawn) in their first lactation, kept at the Institute of Genetics and Animal Biotechnology Polish Academy of Sciences. MSCs were isolated from milk and gene expression was analyzed using Goat Gene Expression microarray. The results were verified by RT-qPCR for five genes (DUSP26, PRLR, SCARA3, APBB2, OR4F4). Statistical analysis was performed in Gene Spring 12 software. Results: Microarrays showed reduced expression of DUSP26, PRLR, SCARA3, APBB2 and OR4F4 genes in SRLV-SP goats. RT-qPCR confirmed changes for DUSP26, SCARA3 and APBB2. Functional analysis indicated associations with immune processes and HIV-like pathways. Discussion: The results suggest that SRLV induces transcriptomic perturbations, especially in immunity-related genes. MSCs are an effective model for non-invasive studies, and further studies may support strategies for combating CAE.
Project description:Dengue represents one of the most serious life-threatening vector-borne infectious diseases that afflict ~50 million people across the globe annually. Whilst symptomatic infections are frequently reported, asymptomatic dengue largely remain unnoticed. The immune correlates conferring protection to individuals that remain clinically asymptomatic have seldom been investigated. We determined the gene expression profiles of host immune factors in individuals with asymptomatic infections, and whose cognate household members showed symptoms and signs consistent to clinical dengue infection. Results provide insight in association of certain host genes to protection against clinical dengue. Blood samples were collected from Dengue Fever (DF) and Dengue Haemorrhagic Fever (DHF) patients in Malaysia who were admitted to university of Malaya Medical Centre (UMMC), Ampang Hospital (AmpangHospital), and Hospital Tengku Ampuan Rahimah (HTAR) Klang. Blood from their asymptomatic household members were also collected. Their peripheral blood mononuclear cells (PBMCs) were isolated. 29 sample pairs (SP) of dengue patients and their accompanying asymptomatic household members were chosen on the following basis for two-channel microarray experiments: patients who have shown positive results for DENV infection with at least 2 diagnostics tests indicating positivity. Positive results for the IgM-captured ELISA were P/N ratio more than 2.0, while total antibody titer of more than 1:2560 or 4 fold increase from acute to convalescence phase was considered positive in HI assay. PRNT, a neutralization test, was used as a measure for levels of neutralizing antibodies and was considered high when it was more than 1:640, based on a reduction neutralization of 50%.
Project description:Teplizumab is approved for delay of diagnosis of type 1 diabetes and modulates new onset disease. Compared to EBV seronegative patients, those who were EBV seropositive prior to treatment had a more robust response to drug in two clinical trials. We compared the phenotypes, transcriptomes, and development of peripheral blood cells before and after teplizumab treatment. Higher number of Tregs and “partially exhausted” CD8+ T cells were found in EBV seropositive individuals at the baseline in the TN10 and AbATE trials. Single cell transcriptomics and functional assays identified downregulation of NFB and other pathways after treatment in treated EBV seropositive patients. Among diabetes antigen specific CD8+ T cells, T cell receptor and mTOR signaling were also reduced. Impairments in function of adaptive immune cells were enhanced by teplizumab treatment in EBV seropositive individuals. Our data indicate that EBV can impair signaling pathways in immune cells, that broadly redirect cell differentiation.