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J Infect Dis. 2018 Mar 28;217(8):1318-1322. doi: 10.1093/infdis/jiy006.

Prospective Discrimination of Controllers From Progressors Early After Low-Dose Mycobacterium tuberculosis Infection of Cynomolgus Macaques using Blood RNA Signatures.

Author information

1
The Center for Infectious Disease Research, Seattle, Washington.
2
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pennsylvania.
3
Baylor Institute for Immunology Research, Dallas, Texas.
4
Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pennsylvania.

Abstract

The cynomolgus macaque model of low-dose Mycobacterium tuberculosis infection recapitulates clinical aspects of human tuberculosis pathology, but it is unknown whether the 2 systems are sufficiently similar that host-based signatures of tuberculosis will be predictive across species. By blind prediction, we demonstrate that a subset of genes comprising a human signature for tuberculosis risk is simultaneously predictive in humans and macaques and prospectively discriminates progressor from controller animals 3-6 weeks after infection. Further analysis yielded a 3-gene signature involving PRDX2 that predicts tuberculosis progression in macaques 10 days after challenge, suggesting novel pathways that define protective responses to M. tuberculosis.

PMID:
29325117
PMCID:
PMC6018950
[Available on 2019-03-28]
DOI:
10.1093/infdis/jiy006

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