Gene expression and TB pathogenesis in rhesus macaques: TR4, CD40, CD40L, FAS (CD95), and TNF are host genetic markers in peripheral blood mononuclear cells that are associated with severity of TB lesions

Morteza Roodgar, Cody T. Ross, Ross Tarara, Linda J Lowenstine, Satya Dandekar, David Glenn Smith

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Tuberculosis (TB) pathologic lesions in rhesus macaques resemble those in humans. The expression levels of several host TB candidate genes in the peripheral blood mononuclear cells (PBMCs) of six rhesus macaques experimentally infected with Mycobacterium tuberculosis were quantified pre-infection and at several dates post-infection. Quantitative measures of TB histopathology in the lungs including: granuloma count, granuloma size, volume of granulomatous and non-granulomatous lesions, and direct bacterial load, were used as the outcomes of a multi-level Bayesian regression model in which expression levels of host genes at various dates were used as predictors. The results indicate that the expression levels of TR4, CD40, CD40L, FAS (CD95) and TNF in PBMC were associated with quantitative measures of the severity of TB histopathologic lesions in the lungs of the study animals. Moreover, no reliable association between the expression levels of IFNE in PBMCs and the severity of TB lesions in the lungs of the study animals was found. In conclusion, PBMC expression profiles derived from the above-listed host genes might be appropriate biomarkers for probabilistic diagnosis and/or prognosis of TB severity in rhesus macaques.

Original languageEnglish (US)
Pages (from-to)396-409
Number of pages14
JournalInfection, Genetics and Evolution
Volume36
DOIs
StatePublished - Dec 1 2015

Fingerprint

CD40 Ligand
tuberculosis
genetic marker
mononuclear leukocytes
Macaca mulatta
Genetic Markers
lesion
lesions (animal)
gene expression
Blood Cells
Tuberculosis
pathogenesis
blood
Gene Expression
genetic markers
lungs
granuloma
Granuloma
Lung
gene

Keywords

  • Gene expression
  • Histopathologic lesions
  • Host genes
  • IFNE
  • Rhesus macaques
  • TR4
  • Tuberculosis (TB)

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Molecular Biology
  • Microbiology
  • Infectious Diseases
  • Microbiology (medical)

Cite this

@article{c857d169a3a94116a538f9def93de519,
title = "Gene expression and TB pathogenesis in rhesus macaques: TR4, CD40, CD40L, FAS (CD95), and TNF are host genetic markers in peripheral blood mononuclear cells that are associated with severity of TB lesions",
abstract = "Tuberculosis (TB) pathologic lesions in rhesus macaques resemble those in humans. The expression levels of several host TB candidate genes in the peripheral blood mononuclear cells (PBMCs) of six rhesus macaques experimentally infected with Mycobacterium tuberculosis were quantified pre-infection and at several dates post-infection. Quantitative measures of TB histopathology in the lungs including: granuloma count, granuloma size, volume of granulomatous and non-granulomatous lesions, and direct bacterial load, were used as the outcomes of a multi-level Bayesian regression model in which expression levels of host genes at various dates were used as predictors. The results indicate that the expression levels of TR4, CD40, CD40L, FAS (CD95) and TNF in PBMC were associated with quantitative measures of the severity of TB histopathologic lesions in the lungs of the study animals. Moreover, no reliable association between the expression levels of IFNE in PBMCs and the severity of TB lesions in the lungs of the study animals was found. In conclusion, PBMC expression profiles derived from the above-listed host genes might be appropriate biomarkers for probabilistic diagnosis and/or prognosis of TB severity in rhesus macaques.",
keywords = "Gene expression, Histopathologic lesions, Host genes, IFNE, Rhesus macaques, TR4, Tuberculosis (TB)",
author = "Morteza Roodgar and Ross, {Cody T.} and Ross Tarara and Lowenstine, {Linda J} and Satya Dandekar and Smith, {David Glenn}",
year = "2015",
month = "12",
day = "1",
doi = "10.1016/j.meegid.2015.10.010",
language = "English (US)",
volume = "36",
pages = "396--409",
journal = "Infection, Genetics and Evolution",
issn = "1567-1348",
publisher = "Elsevier",

}

TY - JOUR

T1 - Gene expression and TB pathogenesis in rhesus macaques

T2 - TR4, CD40, CD40L, FAS (CD95), and TNF are host genetic markers in peripheral blood mononuclear cells that are associated with severity of TB lesions

AU - Roodgar, Morteza

AU - Ross, Cody T.

AU - Tarara, Ross

AU - Lowenstine, Linda J

AU - Dandekar, Satya

AU - Smith, David Glenn

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Tuberculosis (TB) pathologic lesions in rhesus macaques resemble those in humans. The expression levels of several host TB candidate genes in the peripheral blood mononuclear cells (PBMCs) of six rhesus macaques experimentally infected with Mycobacterium tuberculosis were quantified pre-infection and at several dates post-infection. Quantitative measures of TB histopathology in the lungs including: granuloma count, granuloma size, volume of granulomatous and non-granulomatous lesions, and direct bacterial load, were used as the outcomes of a multi-level Bayesian regression model in which expression levels of host genes at various dates were used as predictors. The results indicate that the expression levels of TR4, CD40, CD40L, FAS (CD95) and TNF in PBMC were associated with quantitative measures of the severity of TB histopathologic lesions in the lungs of the study animals. Moreover, no reliable association between the expression levels of IFNE in PBMCs and the severity of TB lesions in the lungs of the study animals was found. In conclusion, PBMC expression profiles derived from the above-listed host genes might be appropriate biomarkers for probabilistic diagnosis and/or prognosis of TB severity in rhesus macaques.

AB - Tuberculosis (TB) pathologic lesions in rhesus macaques resemble those in humans. The expression levels of several host TB candidate genes in the peripheral blood mononuclear cells (PBMCs) of six rhesus macaques experimentally infected with Mycobacterium tuberculosis were quantified pre-infection and at several dates post-infection. Quantitative measures of TB histopathology in the lungs including: granuloma count, granuloma size, volume of granulomatous and non-granulomatous lesions, and direct bacterial load, were used as the outcomes of a multi-level Bayesian regression model in which expression levels of host genes at various dates were used as predictors. The results indicate that the expression levels of TR4, CD40, CD40L, FAS (CD95) and TNF in PBMC were associated with quantitative measures of the severity of TB histopathologic lesions in the lungs of the study animals. Moreover, no reliable association between the expression levels of IFNE in PBMCs and the severity of TB lesions in the lungs of the study animals was found. In conclusion, PBMC expression profiles derived from the above-listed host genes might be appropriate biomarkers for probabilistic diagnosis and/or prognosis of TB severity in rhesus macaques.

KW - Gene expression

KW - Histopathologic lesions

KW - Host genes

KW - IFNE

KW - Rhesus macaques

KW - TR4

KW - Tuberculosis (TB)

UR - http://www.scopus.com/inward/record.url?scp=84949192304&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84949192304&partnerID=8YFLogxK

U2 - 10.1016/j.meegid.2015.10.010

DO - 10.1016/j.meegid.2015.10.010

M3 - Article

C2 - 26483316

AN - SCOPUS:84949192304

VL - 36

SP - 396

EP - 409

JO - Infection, Genetics and Evolution

JF - Infection, Genetics and Evolution

SN - 1567-1348

ER -