TB-IRIS: Proteomic analysis of in vitro PBMC responses to Mycobacterium tuberculosis and response modulation by dexamethasone
File(s)1-s2.0-S0014480016302878-main.pdf (1.76 MB)
Published version
Author(s)
Type
Journal Article
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.
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.
Date Issued
2017-02-14
Date Acceptance
2017-02-11
Citation
Experimental and Molecular Pathology, 2017, 102 (2), pp.237-246
ISSN
0014-4800
Publisher
Elsevier
Start Page
237
End Page
246
Journal / Book Title
Experimental and Molecular Pathology
Volume
102
Issue
2
Copyright Statement
© 2017 The Francis Crick Institute. Published by Elsevier
Inc. This is an open access article under the CC BY license
(
http://creativecommons.org/licenses/by/4.0/
)
Inc. This is an open access article under the CC BY license
(
http://creativecommons.org/licenses/by/4.0/
)
Subjects
Oncology & Carcinogenesis
1103 Clinical Sciences
Notes
publisher: Elsevier articletitle: TB-IRIS: Proteomic analysis of in vitro PBMC responses to Mycobacterium tuberculosis and response modulation by dexamethasone journaltitle: Experimental and Molecular Pathology articlelink: http://dx.doi.org/10.1016/j.yexmp.2017.02.008 content_type: article copyright: © 2017 The Francis Crick Institute. Published by Elsevier Inc.
Publication Status
Published