The role of monocytes in the development of Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome

Tran, Huyen Thi Thanh; Bergh, Rafaël Van den; Vu, Trung Nghia; Laukens, Kris; Worodria, William; Loembé, Marguerite Massinga; Colebunders, Robert; Kestens, Luc; Baetseĺier, Patrick De; Raes, Geert

doi:10.1016/j.imbio.2013.07.004

Cited by 51 publications

(44 citation statements)

References 39 publications

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“…Although this difference did not reach statistical significance, it could have shifted the cytokine balance towards the pro-inflammatory side. In line with our findings, TB-IRIS patients from our cohort have previously been shown to have a pro-inflammatory monocyte-gene expression profile that is also perturbed in pattern recognition receptor pathways [45]. Another study previously reported elevated TNFα production during IRIS upon TLR2 stimulation with lipomannan, without an equivalent rise in IL-10 [16].…”

Section: Discussionsupporting

confidence: 90%

Antigen-Specific Interferon-Gamma Responses and Innate Cytokine Balance in TB-IRIS

et al. 2014

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Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB patients receiving antiretroviral therapy (ART). TB-IRIS could be associated with an exaggerated immune response to TB-antigens. We compared the recovery of IFNγ responses to recall and TB-antigens and explored in vitro innate cytokine production in TB-IRIS patients. Methods In a prospective cohort study of HIV-TB co-infected patients treated for TB before ART initiation, we compared 18 patients who developed TB-IRIS with 18 non-IRIS controls matched for age, sex and CD4 count. We analyzed IFNγ ELISpot responses to CMV, influenza, TB and LPS before ART and during TB-IRIS. CMV and LPS stimulated ELISpot supernatants were subsequently evaluated for production of IL-12p70, IL-6, TNFα and IL-10 by Luminex. Results Before ART, all responses were similar between TB-IRIS patients and non-IRIS controls. During TB-IRIS, IFNγ responses to TB and influenza antigens were comparable between TB-IRIS patients and non-IRIS controls, but responses to CMV and LPS remained significantly lower in TB-IRIS patients. Production of innate cytokines was similar between TB-IRIS patients and non-IRIS controls. However, upon LPS stimulation, IL-6/IL-10 and TNFα/IL-10 ratios were increased in TB-IRIS patients compared to non-IRIS controls. Conclusion TB-IRIS patients did not display excessive IFNγ responses to TB-antigens. In contrast, the reconstitution of CMV and LPS responses was delayed in the TB-IRIS group. For LPS, this was linked with a pro-inflammatory shift in the innate cytokine balance. These data are in support of a prominent role of the innate immune system in TB-IRIS.

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Section: Discussionsupporting

confidence: 90%

Antigen-Specific Interferon-Gamma Responses and Innate Cytokine Balance in TB-IRIS

et al. 2014

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“…Although other innate immune cell types, including NK cells and γ/δ T cells, have been linked to TB-IRIS development [15, 31], it is becoming increasingly clear that myeloid cells play a major part in this syndrome [32]. Our finding that plasma IL-1β levels are elevated pre-ART and increase significantly post-ART initiation in TB-IRIS patients relative to non-TB-IRIS patients provides the first clear indication that this critical pro-inflammatory mediator plays a role in TB-IRIS.…”

Section: Discussionmentioning

confidence: 99%

TB-IRIS, T-cell activation, and remodeling of the T-cell compartment in highly immunosuppressed HIV-infected patients with TB

Haridas

Pean

Jasenosky

et al. 2015

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Objective To investigate the impact of tuberculosis (TB)-associated immune reconstitution syndrome (IRIS) upon immunological recovery and the T cell compartment after initiation of TB and antiretroviral therapy (ART). Design and methods We prospectively evaluated T cell immunophenotypes by flow cytometry and cytokines by Luminex assays in a subset (n=154) of highly immunosuppressed HIV+ patients with TB from the CAMELIA randomized clinical trial. We compared findings from patients who developed TB-IRIS to findings from patients who did not develop TB-IRIS. Data were evaluated with mixed effect linear regression, Kaplan-Meier estimates, and Wilcoxon rank sum tests, and q-values were calculated to control for multiple comparisons. Results Development of TB-IRIS was associated with significantly greater pre-ART frequencies of HLA-DR+CD45RO+CD4+, CCR5+CD4+, OX40+CD4+, and Fas+ effector memory (EM) CD8+ T cells, and significantly elevated levels of plasma IL-6, IL-1β, IL-8, and IL-10 and viral load. Post-ART initiation, EM CD4+ and Fas+ EM CD4+ T cell frequencies significantly expanded, and central memory (CM) CD4+ T cell frequencies significantly contracted in patients who experienced TB-IRIS. By week 34 post-TB treatment initiation, EM/CM CD4+ T cell ratios were markedly higher in TB-IRIS versus non-TB-IRIS patients. Conclusions A distinct pattern of pre-ART T cell and cytokine markers appear to poise the immune response to develop TB-IRIS. Experience of TB-IRIS is then associated with long-term remodeling of the CD4+ T cell memory compartment towards an EM-dominated phenotype. We speculate that these pre- and post-ART TB-IRIS-associated immune parameters may contribute to superior immune control of TB/HIV co-infection and better clinical outcome.

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“…Several studies indicate that circulating immune cells are activated and recruited to the M. tuberculosis-infected lungs to form the granuloma where the M. tuberculosis proliferation is controlled by an active interaction of lymphocytes and infected macrophages [15][16][17][18][19][20]. In a previous study, we observed that peripheral white blood cell (WBC) subpopulation ratios varied according to TB clinical status in a limited number of BCG-vaccinated individuals from an area with a high TB burden [17].…”

Section: Introductionmentioning

confidence: 94%

Biomarkers for risk of developing active tuberculosis in contacts of TB patients: a prospective cohort study

et al. 2015

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Identifying those Mycobacterium tuberculosis latent-infected individuals most at risk of developing active tuberculosis (TB) using routine clinical and laboratory tests remains a huge challenge in TB control efforts. We conducted a prospective longitudinal study of clinical and laboratory markers associated with the risk of developing active TB in contacts with latent M. tuberculosis infection.HIV-negative household contacts (n=296) of pulmonary TB patients underwent monitoring of clinical features, full blood cell counts, tuberculin skin text (TST) and chest radiography performed regularly during 18 months of follow-up. Paired statistical tests, a Kaplan-Meier analysis and Cox proportional hazard modelling were performed on variables between contacts progressing or not progressing to active TB.The appearance of TB disease symptoms in contacts was significantly associated with an elevated peripheral percentage of blood monocytes (adjusted hazard ratio (aHR) 6.25, 95% CI 1.63-23.95; p<0.01), a ⩾14 mm TST response (aHR 5.72, 95% CI 1.22-26.80; p=0.03) and an increased monocyte:lymphocyte ratio (aHR 4.97, 95% CI 1.3-18.99; p=0.03). Among contacts having TST ⩾14 mm, a strong association with risk of progression to TB was found with an elevated blood monocyte percentage (aHR 8.46, p<0.01).Elevated percentage of peripheral blood monocytes plus an elevated TST response are potential biomarkers for identifying contacts of TB patients at highest risk of developing active TB. @ERSpublications Tuberculin skin tests combined with monocyte count improve evaluation of disease progression risk among TB contacts

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The role of monocytes in the development of Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome

Cited by 51 publications

References 39 publications

Antigen-Specific Interferon-Gamma Responses and Innate Cytokine Balance in TB-IRIS

Antigen-Specific Interferon-Gamma Responses and Innate Cytokine Balance in TB-IRIS

TB-IRIS, T-cell activation, and remodeling of the T-cell compartment in highly immunosuppressed HIV-infected patients with TB

Biomarkers for risk of developing active tuberculosis in contacts of TB patients: a prospective cohort study

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