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Expression profiling of lymph nodes in tuberculosis patients reveal inflammatory milieu at site of infection
- Source :
- Scientific Reports
- Publication Year :
- 2015
-
Abstract
- Extrapulmonary manifestations constitute 15 to 20% of tuberculosis cases, with lymph node tuberculosis (LNTB) as the most common form of infection. However, diagnosis and treatment advances are hindered by lack of understanding of LNTB biology. To identify host response, Mycobacterium tuberculosis infected lymph nodes from LNTB patients were studied by means of transcriptomics and quantitative proteomics analyses. The selected targets obtained by comparative analyses were validated by quantitative PCR and immunohistochemistry. This approach provided expression data for 8,728 transcripts and 102 proteins, differentially regulated in the infected human lymph node. Enhanced inflammation with upregulation of T-helper1-related genes, combined with marked dysregulation of matrix metalloproteinases, indicates tissue damage due to high immunoactivity at infected niche. This expression signature was accompanied by significant upregulation of an immunoregulatory gene, leukotriene A4 hydrolase, at both transcript and protein levels. Comparative transcriptional analyses revealed LNTB-specific perturbations. In contrast to pulmonary TB-associated increase in lipid metabolism, genes involved in fatty-acid metabolism were found to be downregulated in LNTB suggesting differential lipid metabolic signature. This study investigates the tissue molecular signature of LNTB patients for the first time and presents findings that indicate the possible mechanism of disease pathology through dysregulation of inflammatory and tissue-repair processes.
- Subjects :
- Adult
Male
Proteomics
Adolescent
Biology
Tuberculosis, Lymph Node
Real-Time Polymerase Chain Reaction
Article
Mycobacterium tuberculosis
Transcriptome
Th2 Cells
Downregulation and upregulation
medicine
Humans
Lymph Node Tuberculosis
Child
Lymph node
Epoxide Hydrolases
Multidisciplinary
Gene Expression Profiling
Fatty Acids
Th1 Cells
biology.organism_classification
Lipid Metabolism
Immunohistochemistry
Matrix Metalloproteinases
Gene expression profiling
medicine.anatomical_structure
Real-time polymerase chain reaction
Immunology
Cytokines
Female
Lymph
Lymph Nodes
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 5
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....efb607aed291203bd88fb21a6b2041a8