TY - JOUR
T1 - Innate immunity and metal ion trafficking pathway perturbations in idiopathic Parkinson's disease and Tuberculosis
T2 - A comparative transcriptomics approach
AU - Vavougios, George D
AU - Zarogiannis, Sotirios
AU - Barh, Debmalya
AU - Breza, Marianthi
AU - Krogfelt, Karen A
AU - Stamoulis, George
AU - Gourgoulianis, Konstantinos I
PY - 2021
Y1 - 2021
N2 - Introduction: The purpose of our study is to detect and compare common, significantly enriched pathways in peripheral blood mononuclears (PBMC) and CNS tissue donated by idiopathic Parkinson's Disease (iPD) patients and compare their transcriptomic profiles with those donated by tuberculosis (TB) patients. Methods: We performed comparative transcriptomic analyses between gene expression studies published in the GEO Datasets repository, retrieved as queries of iPD and TB each vs healthy controls. Results: Datasets retrieved involved iPD: 2 PBMC studies, 1 Substantia Nigra (SN) and 1 Dorsal Motor Nucleus of the Vagus (DMNV) study, as well as TB: 1 PBMC and one study with monocyte (Mc) gene expression profiles. Among significantly enriched pathways were the influenza A (IAV) associated “Viral mRNA Translation” and “L13a-mediated translational silencing of Ceruloplasmin expression”, common between DMNV, active Tb Monocytes (TBA Mc), post-treatment TB and both iPD PBMC datasets. Discussion: Our results support the hypothesis that remnant, postinfectious epigenetic changes on PBMCs inflicted by Mycobacterium Tuberculosis (Mtb) may alter their phenotype, facilitating non-abortive intracellular residency for a subsequent pathogen. This pathogen may be transmissible to the CNS via sites such as the vagal projections, and prime iPD pathogenesis by disrupting metal ion homeostasis in a lifecycle – dependent manner.
AB - Introduction: The purpose of our study is to detect and compare common, significantly enriched pathways in peripheral blood mononuclears (PBMC) and CNS tissue donated by idiopathic Parkinson's Disease (iPD) patients and compare their transcriptomic profiles with those donated by tuberculosis (TB) patients. Methods: We performed comparative transcriptomic analyses between gene expression studies published in the GEO Datasets repository, retrieved as queries of iPD and TB each vs healthy controls. Results: Datasets retrieved involved iPD: 2 PBMC studies, 1 Substantia Nigra (SN) and 1 Dorsal Motor Nucleus of the Vagus (DMNV) study, as well as TB: 1 PBMC and one study with monocyte (Mc) gene expression profiles. Among significantly enriched pathways were the influenza A (IAV) associated “Viral mRNA Translation” and “L13a-mediated translational silencing of Ceruloplasmin expression”, common between DMNV, active Tb Monocytes (TBA Mc), post-treatment TB and both iPD PBMC datasets. Discussion: Our results support the hypothesis that remnant, postinfectious epigenetic changes on PBMCs inflicted by Mycobacterium Tuberculosis (Mtb) may alter their phenotype, facilitating non-abortive intracellular residency for a subsequent pathogen. This pathogen may be transmissible to the CNS via sites such as the vagal projections, and prime iPD pathogenesis by disrupting metal ion homeostasis in a lifecycle – dependent manner.
KW - Mycobacteria
KW - Parkinson's disease
KW - Pathway Enrichment
KW - Systems Biology
KW - Tuberculosis
U2 - 10.1016/j.dscb.2021.100025
DO - 10.1016/j.dscb.2021.100025
M3 - Journal article
VL - 4
JO - Brain Disorders
JF - Brain Disorders
IS - 4
M1 - 100025
ER -