Project description:This study aims to comprehensively investigate the immunological responses associated with non-tuberculous mycobacterial pulmonary disease (NTM-PD). We evaluated immune-related gene expression profiles using nCounter assays on peripheral blood mononuclear cell samples from 18 patients diagnosed with NTM-PD, comparing them with samples from 6 healthy controls.
Project description:The factors predisposing towards the development of pulmonary non-tuberculous mycobacterial disease (pNTM) and influencing disease progression remain unclear. Impaired immune responses have been reported in individuals with pNTM but data are limited and inconsistent. This study aimed to use gene expression profiling to examine the host response to pNTM. Microarray analysis of whole blood gene expression was performed on 25 subjects with pNTM and 27 uninfected controls with respiratory disease. Gene expression results were compared to phenotypic variables and survival data. Compared with uninfected controls, pNTM was associated with down-regulation of 213 transcripts enriched for terms related to T cell signalling including IFNG. Reduced IFNG expression was associated with more severe CT changes and impaired lung function. Mortality was associated with the expression of transcripts related to the innate immune response and inflammation, whereas transcripts related to T and B cell function were associated with improved survival. These findings suggest that pNTM is associated with an aberrant immune response which may reflect an underlying propensity to infection, or result from NTM infection itself. There were important differences in the immune response associated with survival and mortality in pNTM.
Project description:<p>This project aims at characterizing the human host susceptibility to pulmonary non-tuberculous mycobacterial (PNTM) infections. PNTM infections occur in patients with chronic lung disease, but also in a distinct group of elderly women without lung defects but who share a common body morphology: tall and lean with scoliosis, pectus excavatum, and mitral valve prolapse. We performed whole exome and genome sequencing in extended families of patients with active PNTM. This unique collection of familial cohorts in PNTM represents an important opportunity for a high yield search for genes that regulate mucosal immunity. We also sequenced the genome of mycobacterial isolates from PNTM patients to integrate host PNTM susceptibility with mycobacterial genotypes and gain insights into the key factors involved in this devastating disease.</p>
Project description:Tuberculosis and non-tuberculous mycobacterial (NTM) diseases are infections caused by Mycobacterium tuberculosis and non-tuberculous mycobacteria, leading to the formation of granulomatous lesions with caseous necrosis in the lungs. We applied spatial transcriptomics at single-cell resolution (CosMx Spatial Molecular Imaging) to human lung samples from patients with mycobacterial infections. RNA-seq was also performed on the samples.
Project description:Tuberculosis and non-tuberculous mycobacterial (NTM) diseases are infections caused by Mycobacterium tuberculosis and non-tuberculous mycobacteria, leading to the formation of granulomatous lesions with caseous necrosis in the lungs. We applied spatial transcriptomics at single-cell resolution (CosMx Spatial Molecular Imaging) to human lung samples from patients with mycobacterial infections. RNA-seq was also performed on the samples.
Project description:Tuberculous meningitis is one of the fatal forms of extra pulmonary disease associated with high mortality and severe neurological defects in affected individuals. We have carried out transcriptome level analysis using whole human genome microarrays to identify differential expression of genes between tuberculous meningitis and normals. In our gene expression analysis, we found 2,434 genes that were differentially erexpressed with 2 or more than 2 fold changes between tuberculous meningitis compared to normal cases. Most of the genes encoded many of the proteins, which involves metabolism, energy pathways, cell growth and/or maintenance, transport and cell communication and signal transduction. We have performed immunohistochemistry for the validation of some of the novel candidates identified in our microarray studies.!Series_overall_design = Present study carried out mRNA expression profiling of five samples from patients diagnosed with tuberculous meningitis and four head injury cases were used as controls. We have used 4X44K arrays from agilent plaform. To validate our microarray results, we have done Immunohistochemistry on 15 TBM cases with control groups. Present study carried out mRNA expression profiling of five samples from patients diagnosed with tuberculous meningitis and four head injury cases were used as controls. We have used 4X44K arrays from agilent plaform. To validate our microarray results, we have done Immunohistochemistry on 15 TBM cases with control groups.!Series_type = Expression profiling by array
Project description:Tuberculous meningitis is one of the fatal forms of extra pulmonary disease associated with high mortality and severe neurological defects in affected individuals. We have carried out transcriptome level analysis using whole human genome microarrays to identify differential expression of genes between tuberculous meningitis and normals. In our gene expression analysis, we found 2,434 genes that were differentially erexpressed with 2 or more than 2 fold changes between tuberculous meningitis compared to normal cases. Most of the genes encoded many of the proteins, which involves metabolism, energy pathways, cell growth and/or maintenance, transport and cell communication and signal transduction. We have performed immunohistochemistry for the validation of some of the novel candidates identified in our microarray studies.!Series_overall_design = Present study carried out mRNA expression profiling of five samples from patients diagnosed with tuberculous meningitis and four head injury cases were used as controls. We have used 4X44K arrays from agilent plaform. To validate our microarray results, we have done Immunohistochemistry on 15 TBM cases with control groups.
Project description:Tuberculosis (TB) and non-tuberculous mycobacterial (NTM) infections, though clinically similar, require distinct management, highlighting the need for reliable biomarkers to differentiate them. In a study of 108 patients, 16S rRNA sequencing revealed distinct microbial signatures, with Enterococcus faecalis, Streptococcus mutans, and Snodgrassella alvi associated with TB, and Cardiobacterium hominis and Prevotella nigrescens linked to NTM. The absence of Mobiluncus curtisii, particularly with Olsenella phocaeensis also absent, suggested a higher probability of NTM, offering promising insights for diagnostic and therapeutic advancements.