TB-IRIS: proteomic analysis of in vitro PMBC responses to mycobacterium tuberculosis and response modulation by dexamethasone
SOURCE: Experimental and Molecular Pathology
OUTPUT TYPE: Journal Article
PUBLICATION YEAR: 2017
TITLE AUTHOR(S): L.Bell, J.M.Peyper, S.Garnett, R.Tadokera, R.Wilkinson, G.Meintjies, J.M.Blackburn
KEYWORDS: TUBERCULOSIS
DEPARTMENT: Public Health, Societies and Belonging (HSC)
Print: HSRC Library: shelf number 9715
HANDLE: 20.500.11910/10861
URI: http://hdl.handle.net/20.500.11910/10861
OUTPUT TYPE: Journal Article
PUBLICATION YEAR: 2017
TITLE AUTHOR(S): L.Bell, J.M.Peyper, S.Garnett, R.Tadokera, R.Wilkinson, G.Meintjies, J.M.Blackburn
KEYWORDS: TUBERCULOSIS
DEPARTMENT: Public Health, Societies and Belonging (HSC)
Print: HSRC Library: shelf number 9715
HANDLE: 20.500.11910/10861
URI: http://hdl.handle.net/20.500.11910/10861
If you would like to obtain a copy of this Research Output, please contact Hanlie Baudin at researchoutputs@hsrc.ac.za.
Abstract
Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome(TB-IRIS) occurs in 8???54% of South African patients undergoing treatment for tuberculosis/human immunodeficiency virus co-infection. Improved TB-IRIS molecular pathogenesis understanding would enhance risk stratification, diagnosis, prognostication, and treatment. We assessed how TB-IRIS status and dexamethasone influence leukocyte proteomic responses to Mycobacterium tuberculosis (Mtb). Patient blood was obtained three weeks post-anti-retroviral therapy initiation. Isolated mononuclear cells were stimulated ex vivo with heat-killed Mtb in the presence/absence of dexamethasone. Mass spectrometry-based proteomic comparison of TB-IRIS and non-IRIS patient-derived cells facilitated generation of hypotheses regarding pathogenesis. Few represented TB-IRIS-group immune-related pathways achieved significant activation, with relative underutilisation of ???inter-cellular interaction??? and ???Fc?? receptor-mediated phagocytosis??? (but a tendency towards apoptosis-related) pathways. Dexamethasone facilitated significant activation of innate-related pathways. Differentially-expressed non-IRIS-group proteins suggest focused and co-ordinated immunological pathways, regardless of dexamethasone status. Findings suggest a relative deficit in TB-IRIS-group responses to and clearance of Mtb antigens, ameliorated by dexamethasone.-
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