ArticleBMC infectious diseases2015
Monocyte unresponsiveness and impaired IL1β, TNFα and IL7 production are associated with a poor outcome in Malawian adults with pulmonary tuberculosis.
Article in BMC infectious diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Systemic Host Proteomic Signatures as Dynamic Markers for Monitoring Pulmonary Tuberculosis Treatment Response.Infection and drug resistance · 2026Review
- TCA metabolism regulates DNA hypermethylation in LPS andProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- New Insights into Biomarkers for Evaluating Therapy Efficacy in Pulmonary Tuberculosis: A Narrative Review.Infectious diseases and therapy · 2023Review
- Xpert Ultra testing of blood in severe HIV-associated tuberculosis to detect and measure Mycobacterium tuberculosis blood stream infection: a diagnostic and disease biomarker cohort study.The Lancet. Microbe · 2022Article
- Hif-1α-Induced Expression of Il-1β Protects against Mycobacterial Infection in Zebrafish.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Disparate Tuberculosis Disease Development in Macaque Species Is Associated With Innate Immunity.Frontiers in immunology · 2019Article
- Upregulation of miR-196b-5p attenuates BCG uptake via targeting SOCS3 and activating STAT3 in macrophages from patients with long-term cigarette smoking-related active pulmonary tuberculosis.Journal of translational medicine · 2018Article
- Diminished plasma levels of common γ-chain cytokines in pulmonary tuberculosis and reversal following treatment.PloS one · 2017Article
- Recombinant human lactoferrin modulates human PBMC derived macrophage responses to BCG and LPS.Tuberculosis (Edinburgh, Scotland) · 2016Article
- Tuberculosis-sensitized monocytes sustain immune response of interleukin-37.Molecular immunology · 2016Article
- Article
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundEarly death during TB treatment is associated with depressed TNFα response to antigenic stimulation and propensity to superadded bacterial infection. Hypothesising the role of monocyte unresponsiveness, we further compared the immunological profile between patients who died or suffered a life-threatening deterioration ('poor outcome') during the intensive phase of TB treatment with patients who had an uneventful clinical course ('good outcome') who had been recruited as part of a larger prospective cohort study of Malawian TB patients.
methodsUsing Luminex, IL1β, IL2, IL4, IL5, IL6, IL7, IL8, IL10, IL12, IL13, IL17, GCSF, GMCSF, MCP1, MIP1b, IFNγ and TNFα were measured in whole blood assay supernatants (stimulated with Mycobacterium tuberculosis H37Rv and LPS) and serum from 44 Malawian adult TB patients (22 of each outcome) immediately prior to commencing treatment, after 7 days and on day 56 of TB treatment. Monocyte surface expression of CD14, CD16, TLR2, TLR4, CD86 and HLADR, and intracellular TNFα were measured by flow cytometry as was intracellular TNFα response to purified TLR ligands.
resultsLower TB antigen-induced IL1β (p = 0.006), TNFα (p = 0.02) and IL7 (p = 0.009) were produced in the poor outcome group. TNFα was produced by 'classical' CD14(hi)CD16(lo) monocytes, with no correlation between this response and expression of monocyte surface markers. Response to TB antigens correlated with responses to the purified TLR 2, 3 and 4 ligands.
conclusionsDysregulated monocyte cytokine production was identified in TB patients with poor outcome. Lower TNFα responses to H37Rv paralleled lower responses to a panel of TLR ligands, suggesting an underlying perturbation in common TLR signalling pathways. Future work should explore the role of TLR polymorphisms in immune response and clinical outcome in TB patients.
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