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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

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 experimentally infected (Mycobacterium tuberculosis) rhesus macaques were quantified pre-infection and at several time points 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 time points were used as predictors. The results indicate that the expression levels of NR2C2(TR4), CD40, CD40L, Fas (CD95) and TNF-alpha 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 IFN-epsilon 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.

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Bibtex:

@article{Roodgar2015396,
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 ",
journal = "Infection, Genetics and Evolution ",
volume = "36",
number = "",
pages = "396 - 409",
year = "2015",
note = "",
doi = "http://dx.doi.org/10.1016/j.meegid.2015.10.010",
author = "Morteza Roodgar and Cody T. Ross and Ross Tarara and Linda Lowenstine and Satya Dandekar and David Glenn Smith"
}

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