1. TB-IRIS: Proteomic analysis of in vitro PBMC responses to Mycobacterium tuberculosis and response modulation by dexamethasone.
- Author
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Bell, Liam, Peyper, Janique M., Garnett, Shaun, Tadokera, Rabecca, Wilkinson, Robert, Meintjes, Graeme, and Blackburn, Jonathan M.
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IMMUNE reconstitution inflammatory syndrome , *MYCOBACTERIUM tuberculosis , *PROTEOMICS , *DEXAMETHASONE , *SOUTH Africans , *MOLECULAR biology , *DISEASES - 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 under-utilisation of “inter-cellular interaction” and “Fcγ 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. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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