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Interleukin 1-beta (IL-1β) production by innate cells following TLR stimulation correlates with TB recurrence in ART-treated HIV infected patients
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Feb 01 2017
Source: J Acquir Immune Defic Syndr. 74(2):213-220. -
Alternative Title:J Acquir Immune Defic Syndr
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Personal Author:
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Description:Background
Tuberculosis (TB) remains a major cause of global morbidity and mortality, especially in the context of HIV co-infection, since immunity is not completely restored following antiretroviral therapy (ART). The identification of immune correlates of risk for TB disease could help in the design of host-directed therapies and clinical management. This study aimed to identify innate immune correlates of TB recurrence in HIV+ ART-treated individuals with a history of previous successful TB treatment.
Methods
Twelve participants with a recurrent episode of TB (cases) were matched for age, sex, time on ART, pre-ART CD4 count with 12 participants who did not develop recurrent TB in 60 months of follow-up (controls). Cryopreserved peripheral blood mononuclear cells from time points prior to TB recurrence were stimulated with ligands for Toll like receptors (TLR) including TLR-2, TLR-4, and TLR-7/8. Multi-color flow cytometry and intracellular cytokine staining was used to detect IL-1β, TNF-α, IL-12 and IP10 responses from monocytes and myeloid dendritic cells (mDCs).
Results
Elevated production of IL-1β from monocytes following TLR-2, TLR-4 and TLR-7/8 stimulation was associated with reduced odds of TB recurrence. In contrast, production of IL-1β from both monocytes and mDCs following Bacillus Calmette-Guérin (BCG) stimulation was associated with increased odds of TB recurrence (risk of recurrence increased by 30% in monocytes and 42% in mDCs respectively).
Conclusion
Production of IL-1β by innate immune cells following TLR and BCG stimulations correlated with differential TB recurrence outcomes in ART-treated patients and highlights differences in host response to TB.
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Pubmed ID:27654812
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Pubmed Central ID:PMC5237660
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