Peripheral blood gamma interferon release assays predict lung responses and Mycobacterium tuberculosis disease outcome in mice

Clinical and Vaccine Immunology : CVI
Gillian L BeamerJoanne Turner

Abstract

Current diagnostic tests for tuberculosis (TB) are not able to distinguish active disease from latent Mycobacterium tuberculosis infection, nor are they able to quantify the risk of a latently infected person progressing to active TB. There is interest, however, in adapting antigen-specific gamma interferon (IFN-gamma) release assays (IGRAs) to predict disease outcome. In this study, we used the differential susceptibilities of inbred mouse strains to M. tuberculosis infection to evaluate the prognostic capabilities of IGRAs. Using lung and blood cultures, we determined that CBA/J, DBA/2, and C3H/HeJ mice (models of heightened risk of progression to active TB) produced less antigen-specific IFN-gamma in response to M. tuberculosis culture filtrate proteins and early secreted antigenic target-6 than the relatively resistant C57BL/6 mouse strain. Additionally, reduced IFN-gamma secretion in supernatants reflected a reduced frequency of IFN-gamma-responding cells in the lung and blood and not a specific defect in IFN-gamma secretion at the single-cell level. Importantly, detection of antigen-specific IFN-gamma from blood cultures accurately reflected lung responses, indicating that blood can be an appropriate test tissue in humans...Continue Reading

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Citations

Oct 11, 2011·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·J E M de SteenwinkelI A J M Bakker-Woudenberg
Apr 8, 2010·Journal of Leukocyte Biology·Bridget VesoskyGillian Beamer
Mar 28, 2013·Veterinary Pathology·S MajorG Beamer
Aug 8, 2015·The European Respiratory Journal·Niaina RakotosamimananaVoahangy Rasolofo Razanamparany
Feb 12, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Joshua C CyktorJoanne Turner
Oct 4, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gillian L BeamerJoanne Turner
Jul 30, 2017·Brain Sciences·Alexandria Hicks-NelsonBenjamin C Nephew
Jul 8, 2021·Microbiology Spectrum·Tucker J PiergalliniJoanne Turner

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