Project description:Metagenomics analysis reveals co-infection of fungi and bacteria isolated from different regions of brain tissue from elderly persons and patients with Alzheimer's disease.
Project description:To investigate the early immune profiles of patients, particularly those with HIV and tuberculosis co-infection, we collected blood samples from three individuals in the HIV/MTB co-infection group, three HIV/AIDS patients, and three healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated, and the MobiNova®-100 Single Cell System (MobiDrop (Zhejiang) Co., Ltd.) was employed to prepare single-cell sequencing libraries. Subsequently, a single-cell RNA expression matrix was generated using the Illumina NovaSeq 6000 System, yielding a total of 113,816 cells for further analysis.
Project description:HIV coinfection impairs Mtb-specific immunity resulting in reactivation of a latent TB infection (LTBI) in a subset of individuals. We performed Single cell RNA sequencing (scRNA-seq) on bronchalvolear lavage (BAL) samples collected at pre-determined time points from Mycobacterium tuberculosis (Mtb)/ Simian Immunodeficiency Virus (SIV) co-infected rhesus macaques. We identified a total of 14 clusters including monocytes, natural killer (NK) cells, T regs, central memory CD4+ T cells, B cells, club cells and neutrophils in the airways of Mtb/SIV co-infected rhesus macaques. Diminished expression of TH1 cell-specific transcription factors after SIV co-infection was not rescued despite effective cART. In contrast, SIV co-infection led to a reduction in the expression of immunoregulators in monocyte clusters; but increased expression of genes involved in interferon signaling, TH17 induction, T cell activation and tuberculosis associated immune reconstitution inflammatory syndrome (TB-IRIS). Increased inflammation and migratory gene expression was observed in dendritic cells upon SIV co-infection. Overall, the lungs of SIV co-infected macaques with LTBI-like controlled, asymptomatic Mtb infection are characterized by the presence of chronic immune activation at the transcriptomic level, which can persist despite cART. Our work identifies key cell subsets, including novel ones, impacted by HIV coinfection of a latent TB infection in a biologically relevant animal model.
Project description:Background and aims: The intrahepatic processes associated with chronic hepatitis B (CHB), especially in the context of HDV and HIV co-infection, require a better understanding. Spatial transcriptomics can provide new insights into the complex intrahepatic biological processes, guiding new personalized treatments. Our aim is to evaluate this method to characterize the hepatic transcriptional landscape, cellular composition and biological pathways in liver biopsy samples from patients infected with HBV and HDV or HIV co-infection. Method: The GeoMx nanostring Digital Spatial Profiling (DSP) platform was employed to assess expression of HBsAg and CD45 in formalin fixed paraffin embedded (FFPE) biopsies from three treatment-naïve patients with chronic HBV and HDV or HIV co-infection. The GeoMx whole transcriptome human atlas assay quantified the expression of genes enriched in specific regions of interest (ROIs). Cell type proportions within ROIs were deconvoluted using a training matrix from the human liver cell atlas. A weighted gene correlation network analysis (WGCNA) evaluated transcriptomic signatures across sampled regions. Results: We identified spatially discrete transcriptomic signatures and distinct biological pathways that associate with HBV infection/disease status and immune responses. Shared features including cytotoxicity and B cell receptor signaling were consistent across patients, suggesting common elements alongside individual traits. HDV/HBV co-infection exhibited upregulated genes linked to apoptosis and immune cell recruitment, whereas HIV/HBV co-infection featured genes related to interferon response regulation. Varied cellular characteristics and immune cell populations, with an abundance of T cells in the HDV/HBV sample, were observed within analyzed regions. Transcriptional differences in hepatocyte function suggest disrupted metabolic processes in HDV/HBV co-infection potentially impacting disease progression. Conclusion: This proof-of-principle study shows the value of this platform in investigating the complex immune landscape highlighting relevant host pathways to disease pathogenesis.
Project description:The aim of this study was to identify differential gene and protein expression associated with GBV-C that may be of importance in reduction of HCV-related liver disease. GB virus C (GBV-C) infection leads to improved outcomes in human immunodeficiency virus (HIV) infection. Furthermore, GBV-C has been shown to reduce hepatitis C virus (HCV)-related liver disease in HCV/HIV co-infection. We aimed to identify differential gene expression associated with GBV-C in HCV/HIV co-infection by comparing RNA expression from liver biopsies of HCV/HIV co-infected patients with and without GBV-C infection. Liver biopsies were obtained from 10 Patients with HCV/HIV co-infection; 4 of these patients were positive for GBV-C infection and 6 were negative for GBV-C infection. The tissue was stored in RNAlater and RNA was extracted for hybridisation to Affymetrix Human Genome U133 plus 2.0 microarrays at the University of Texas Medical Branch Molecular Genomics Core Laboratory. The data was analysed for genes differentially expressed between GBV-C positive and negative patients using Partek Genomics suite and applying a custom CDF file (Hs133P_Hs_UG_8), available from Molecular and Behavioural Neuroscience Institute, University of Michigan.