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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
  • Published Date:
    Feb 01 2017
  • Source:
    J Acquir Immune Defic Syndr. 74(2):213-220.


Public Access Version Available on: February 01, 2018 information icon
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Details:
  • Pubmed ID:
    27654812
  • Pubmed Central ID:
    PMC5237660
  • 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.

  • Document Type:
  • Collection(s):
  • Funding:
    D43 TW000231/TW/FIC NIH HHS/United States
    U19 AI051794/AI/NIAID NIH HHS/United States
    U2G PS001350/PS/NCHHSTP CDC HHS/United States
  • Supporting Files:
    No Additional Files
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