title: Expression profiling of lymph nodes in tuberculosis patients reveal inflammatory milieu at site of infection.
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.
authors.affiliation: CSIR-Institute of Genomics &Integrative Biology, Mall Road, Delhi, India.
authors.forename: Abhijit
authors.initials: A
authors.lastname: Maji
authors.affiliation: CSIR-Institute of Genomics &Integrative Biology, Mall Road, Delhi, India.
authors.forename: Richa
authors.initials: R
authors.lastname: Misra
authors.affiliation: CSIR-Institute of Genomics &Integrative Biology, Mall Road, Delhi, India.|Academy of Scientific &Innovative Research (AcSIR), CSIR-IGIB, Delhi, India.
authors.forename: Anupam
authors.initials: A
authors.lastname: Kumar Mondal
authors.affiliation: CSIR-Institute of Genomics &Integrative Biology, Mall Road, Delhi, India.
authors.forename: Dhirendra
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Department of Zoology, University of Delhi, Delhi, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Bajaj
authors.affiliation: CSIR-Institute of Genomics &Integrative Biology, Mall Road, Delhi, India.
authors.forename: Anshika
authors.initials: A
authors.lastname: Singhal
authors.affiliation: CSIR-Institute of Genomics &Integrative Biology, Mall Road, Delhi, India.
authors.forename: Gunjan
authors.initials: G
authors.lastname: Arora
authors.affiliation: CSIR-Institute of Genomics &Integrative Biology, Mall Road, Delhi, India.
authors.forename: Asani
authors.initials: A
authors.lastname: Bhaduri
authors.affiliation: CSIR-Institute of Genomics &Integrative Biology, Mall Road, Delhi, India.
authors.forename: Andaleeb
authors.initials: A
authors.lastname: Sajid
authors.affiliation: CSIR-Institute of Genomics &Integrative Biology, Mall Road, Delhi, India.
authors.forename: Sugandha
authors.initials: S
authors.lastname: Bhatia
authors.affiliation: Hindu Rao Hospital, Malka Ganj, Delhi, India.
authors.forename: Sompal
authors.initials: S
authors.lastname: Singh
authors.affiliation: Hindu Rao Hospital, Malka Ganj, Delhi, India.
authors.forename: Harshvardhan
authors.initials: H
authors.lastname: Singh
authors.affiliation: CSIR-Institute of Genomics &Integrative Biology, Mall Road, Delhi, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Rao
authors.affiliation: CSIR-Institute of Genomics &Integrative Biology, Mall Road, Delhi, India.
authors.forename: Debasis
authors.initials: D
authors.lastname: Dash
authors.affiliation: Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: E
authors.initials: E
authors.lastname: Baby Shalini
authors.affiliation: Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: Joy
authors.initials: J
authors.lastname: Sarojini Michael
authors.affiliation: Rajan Babu Institute of Pulmonary Medicine and Tuberculosis, Delhi, India.
authors.forename: Anil
authors.initials: A
authors.lastname: Chaudhary
authors.affiliation: CSIR-Institute of Genomics &Integrative Biology, Mall Road, Delhi, India.
authors.forename: Rajesh S
authors.initials: RS
authors.lastname: Gokhale
authors.affiliation: CSIR-Institute of Genomics &Integrative Biology, Mall Road, Delhi, India.
authors.forename: Yogendra
authors.initials: Y
authors.lastname: Singh
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D050356:Lipid Metabolism / Q000235:genetics; D008198:Lymph Nodes / Q000378:metabolism*; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D060888:Real-Time Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D059467:Transcriptome; D014388:Tuberculosis, Lymph Node / Q000378:metabolism / Q000473:pathology*
chemical_list: D016207:Cytokines; D005227:Fatty Acids; D004851:Epoxide Hydrolases; D020782:Matrix Metalloproteinases; C043134:leukotriene A4 hydrolase