GSE84152   Details

GSE Accession GSE84152
Title Early whole blood transcriptional signatures are associated with severity of lung inflammation in cynomolgus macaques with Mycobacterium tuberculosis infection
Submission Date 7/7/16
Last Update Date 10/27/16
Pubmed ID
Experiment Type Expression profiling by array
Contributor Hannah,P,Gideon; Jason,A,Skinner; Nicole Baldwin; JoAnne,L,Flynn; Philana,L,Lin
Contact Name
Contact E-mail
Organization Name
Organism Homo sapiens; Macaca fascicularis
Organism ID 9606; 9541
Organism Synonym man; human; cynomolgus monkey; cynomolgus macaque; Macaca cynomolgus; long-tailed macaque; crab-eating macaque; Macaca irus; cynomolgus monkeys; crab eating macaque
Summary This longitudinal dataset was generated to assess changes in whole blood gene expression following low dose Mycobacterium tuberculosis infection of Cynomolgus macaques. In addition to changes in mRNA transcript abundance, changes in circulating immune cell populations were also assessed using both complete blood counts (CBC) and using flow cytometry. Disease severity was determined using both clinical diagnosis (active vs. latent) and 18F-flurodeoxyglucose (FDG avidity) by 6 months post-infection. The greatest change in transcriptional activity occurred 20-56 days after infection, when the maximum activity of immune related transcripts was observed. After stratifying macaques based on clinical diagnosis, those macaques with active disease exhibited a similar signature to that observed in humans with active TB. However, only modest transcriptional differences between active TB and latently infected macaques were observed. As an alternative stratification approach, the severity of lung inflammation measured by lung FDG avidity was used to separate macaques into high and low FDG groups. Blood transcript activity was highly correlated with lung inflammation at early time points post-infection. The differential expression signatures between animals stratified with high and low lung FDG were stronger than those observed with groups defined by clinical outcome.. Furthermore, gene level analysis of of pre-infection signatures suggest that interferon and inflammation signatures may distinguish eventual clinical outcomes and lung FDG avidity prior infection. In conclusion, this study demonstrates that transcriptional changes in the macaque model recapitulate those observed in human Mtb infection while providing additional insight into the early and pre-infection events associated with disease severity and outcome.
Overall Design In total, the responses of 38 Cynomolgus macaques to low dose Mtb infection (Erdman ~25CFU) were assessed in this study. Blood draws for the assessment of gene expression and cellular composition were assessed at two time points prior to infection (Pre1 and Pre2) and at days: 3,7,10,20,30,42,56,90,120,150,180 post-infection. Binary clinical diagnosis (active v. latent) and lung inflamation (FDG avidity) were both used used to stratify the severity of infection outcome. Those samples that were taken at the time of clinical diagnosis along with the pre-infection control are denoted by Yes in the SynchroSet column.
Platform ID
Timepoint Count 38
Timepoints gsm: [m19, m4, m1, m7, m18, m11, m13, m2, m5, m10, m9, m17, m16, m15, m8, m14, m12, m3, m6, m20, m26, m30, m31, m35, m33, m23, m21, m27, m29, m36, m28, m24, m25, m32, m38, m34, m37, m22]
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