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 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.
Graduate Group of Comparative Pathology, University of California, Davis, United States. Electronic address: mroodgar@ucdavis.edu.
Morteza
M
Roodgar
Department of Anthropology, University of California, Davis, United States.
Cody T
CT
Ross
California National Primate Research Center (CNPRC), University of California Davis, Davis, CA 95616, United States.
Ross
R
Tarara
Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, United States.
Linda
L
Lowenstine
Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA 95616, United States.
Satya
S
Dandekar
Graduate Group of Comparative Pathology, University of California, Davis, United States; Department of Anthropology, University of California, Davis, United States; California National Primate Research Center (CNPRC), University of California Davis, Davis, CA 95616, United States.
David Glenn
DG
Smith
D000818:Animals; D019013:CD40 Antigens / Q000235:genetics; D023201:CD40 Ligand / Q000235:genetics; D016000:Cluster Analysis; D015870:Gene Expression; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D054884:Host-Pathogen Interactions / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008253:Macaca mulatta; D008992:Monkey Diseases / Q000175:diagnosis / Q000235:genetics* / Q000382:microbiology*; D009169:Mycobacterium tuberculosis; D011988:Receptors, Thyroid Hormone / Q000235:genetics; D012720:Severity of Illness Index; D014376:Tuberculosis / Q000662:veterinary*; D048069:Tumor Necrosis Factors / Q000235:genetics; D019014:fas Receptor / Q000235:genetics
D019013:CD40 Antigens; D005819:Genetic Markers; D011988:Receptors, Thyroid Hormone; D048069:Tumor Necrosis Factors; D019014:fas Receptor; D023201:CD40 Ligand
Gene expression; Histopathologic lesions; Host genes; IFNE; Rhesus macaques; TR4; Tuberculosis (TB)