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 language | English (US) |
|---|---|
| Pages (from-to) | 396-409 |
| Number of pages | 14 |
| Journal | Infection, Genetics and Evolution |
| Volume | 36 |
| DOIs | |
| State | Published - Dec 1 2015 |
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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
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. / Roodgar, Morteza; Ross, Cody T.; Tarara, Ross; Lowenstine, Linda J; Dandekar, Satya; Smith, David Glenn.
In: Infection, Genetics and Evolution, Vol. 36, 01.12.2015, p. 396-409.Research output: Contribution to journal › Article
}
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 -