Systems Immunology of Diabetes-Tuberculosis Comorbidity Reveals Signatures of Disease Complications

Abstract Comorbid diabetes mellitus (DM) increases tuberculosis (TB) risk and adverse outcomes but the pathological interactions between DM and TB remain incompletely understood. We performed an integrative analysis of whole blood gene expression and plasma analytes, comparing South Indian TB patien...

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Autores principales:	Cesar A. Prada-Medina, Kiyoshi F. Fukutani, Nathella Pavan Kumar, Leonardo Gil-Santana, Subash Babu, Flávio Lichtenstein, Kim West, Shanmugam Sivakumar, Pradeep A. Menon, Vijay Viswanathan, Bruno B. Andrade, Helder I. Nakaya, Hardy Kornfeld
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c276cbf05b4a4ab5958679ad6d679e41
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spelling	oai:doaj.org-article:c276cbf05b4a4ab5958679ad6d679e412021-12-02T16:07:02ZSystems Immunology of Diabetes-Tuberculosis Comorbidity Reveals Signatures of Disease Complications10.1038/s41598-017-01767-42045-2322https://doaj.org/article/c276cbf05b4a4ab5958679ad6d679e412017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01767-4https://doaj.org/toc/2045-2322Abstract Comorbid diabetes mellitus (DM) increases tuberculosis (TB) risk and adverse outcomes but the pathological interactions between DM and TB remain incompletely understood. We performed an integrative analysis of whole blood gene expression and plasma analytes, comparing South Indian TB patients with and without DM to diabetic and non-diabetic controls without TB. Luminex assay of plasma cytokines and growth factors delineated a distinct biosignature in comorbid TBDM in this cohort. Transcriptional profiling revealed elements in common with published TB signatures from cohorts that excluded DM. Neutrophil count correlated with the molecular degree of perturbation, especially in TBDM patients. Body mass index and HDL cholesterol were negatively correlated with molecular degree of perturbation. Diabetic complication pathways including several pathways linked to epigenetic reprogramming were activated in TBDM above levels observed with DM alone. Our data provide a rationale for trials of host-directed therapies in TBDM, targeting neutrophilic inflammation and diabetic complication pathways to address the greater morbidity and mortality associated with this increasingly prevalent dual burden of communicable and non-communicable diseases.Cesar A. Prada-MedinaKiyoshi F. FukutaniNathella Pavan KumarLeonardo Gil-SantanaSubash BabuFlávio LichtensteinKim WestShanmugam SivakumarPradeep A. MenonVijay ViswanathanBruno B. AndradeHelder I. NakayaHardy KornfeldNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cesar A. Prada-Medina Kiyoshi F. Fukutani Nathella Pavan Kumar Leonardo Gil-Santana Subash Babu Flávio Lichtenstein Kim West Shanmugam Sivakumar Pradeep A. Menon Vijay Viswanathan Bruno B. Andrade Helder I. Nakaya Hardy Kornfeld Systems Immunology of Diabetes-Tuberculosis Comorbidity Reveals Signatures of Disease Complications
description	Abstract Comorbid diabetes mellitus (DM) increases tuberculosis (TB) risk and adverse outcomes but the pathological interactions between DM and TB remain incompletely understood. We performed an integrative analysis of whole blood gene expression and plasma analytes, comparing South Indian TB patients with and without DM to diabetic and non-diabetic controls without TB. Luminex assay of plasma cytokines and growth factors delineated a distinct biosignature in comorbid TBDM in this cohort. Transcriptional profiling revealed elements in common with published TB signatures from cohorts that excluded DM. Neutrophil count correlated with the molecular degree of perturbation, especially in TBDM patients. Body mass index and HDL cholesterol were negatively correlated with molecular degree of perturbation. Diabetic complication pathways including several pathways linked to epigenetic reprogramming were activated in TBDM above levels observed with DM alone. Our data provide a rationale for trials of host-directed therapies in TBDM, targeting neutrophilic inflammation and diabetic complication pathways to address the greater morbidity and mortality associated with this increasingly prevalent dual burden of communicable and non-communicable diseases.
format	article
author	Cesar A. Prada-Medina Kiyoshi F. Fukutani Nathella Pavan Kumar Leonardo Gil-Santana Subash Babu Flávio Lichtenstein Kim West Shanmugam Sivakumar Pradeep A. Menon Vijay Viswanathan Bruno B. Andrade Helder I. Nakaya Hardy Kornfeld
author_facet	Cesar A. Prada-Medina Kiyoshi F. Fukutani Nathella Pavan Kumar Leonardo Gil-Santana Subash Babu Flávio Lichtenstein Kim West Shanmugam Sivakumar Pradeep A. Menon Vijay Viswanathan Bruno B. Andrade Helder I. Nakaya Hardy Kornfeld
author_sort	Cesar A. Prada-Medina
title	Systems Immunology of Diabetes-Tuberculosis Comorbidity Reveals Signatures of Disease Complications
title_short	Systems Immunology of Diabetes-Tuberculosis Comorbidity Reveals Signatures of Disease Complications
title_full	Systems Immunology of Diabetes-Tuberculosis Comorbidity Reveals Signatures of Disease Complications
title_fullStr	Systems Immunology of Diabetes-Tuberculosis Comorbidity Reveals Signatures of Disease Complications
title_full_unstemmed	Systems Immunology of Diabetes-Tuberculosis Comorbidity Reveals Signatures of Disease Complications
title_sort	systems immunology of diabetes-tuberculosis comorbidity reveals signatures of disease complications
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c276cbf05b4a4ab5958679ad6d679e41
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Systems Immunology of Diabetes-Tuberculosis Comorbidity Reveals Signatures of Disease Complications

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