In:
Frontiers in Immunology, Frontiers Media SA, Vol. 15 ( 2024-10-4)
Abstract:
Efforts to eradicate tuberculosis (TB) are threatened by diabetes mellitus (DM), which confers a 3-fold increase in the risk of TB disease. The changes in the memory phenotypes and functional profiles of Mycobacterium tuberculosis ( Mtb )-specific T cells in latent TB infection (LTBI)-DM participants remain poorly characterised. We, therefore, assessed the effect of DM on T-cell phenotype and function in LTBI and DM clinical groups. Methods We compared the memory phenotypes and function profiles of Mtb -specific CD4 + and CD8 + T cells among participants with LTBI-DM (n=21), LTBI-only (n=17) and DM-only (n=16). Peripheral blood mononuclear cells (PBMCs) were stimulated with early secretory antigenic 6 kDa (ESAT-6) and culture filtrate protein 10 (CFP-10) peptide pools or phytohemagglutinin (PHA). The memory phenotypes (CCR7/CD45RA), and functional profiles (HLA-DR, PD-1, CD107a, IFN-γ, IL-2, TNF, IL-13, IL-17A) of Mtb -specific CD4 + and CD8 + T cells were characterised by flow cytometry. Results Naïve CD4 + T cells were significantly decreased in the LTBI-DM compared to the LTBI-only participants [0.47 (0.34-0.69) vs 0.91 (0.59-1.05); (p & lt;0.001)]. Similarly, CD8 + HLA-DR expression was significantly decreased in LTBI-DM compared to LTBI-only participants [0.26 (0.19-0.33) vs 0.52 (0.40-0.64); (p & lt;0.0001)], whereas CD4 + and CD8 + PD-1 expression was significantly upregulated in the LTBI-DM compared to the LTBI-only participants [0.61 (0.53-0.77) vs 0.19 (0.10-0.28); (p & lt;0.0001) and 0.41 (0.37-0.56) vs 0.29 (0.17-0.42); (p=0.007)] respectively. CD4 + and CD8 + IFN-γ production was significantly decreased in the LTBI-DM compared to the LTBI-only participants [0.28 (0.19-0.38) vs 0.39 (0.25-0.53); (p=0.030) and 0.36 (0.27-0.49) vs 0.55 (0.41-0.88); (p=0.016)] respectively. CD4 + TNF and CD8 + IL-17A production were significantly decreased in participants with LTBI-DM compared to those with LTBI-only [0.38 (0.33-0.50) vs 0.62 (0.46-0.87); (p=0.004) and 0.29 (0.16-0.42) vs 0.47 (0.29-0.52); (0.017)] respectively. LTBI-DM participants had significantly lower dual-functional (IFN-γ + IL-2 + and IL-2 + TNF + ) and mono-functional (IFN-γ + and TNF + ) CD4 + responses than LTBI-only participants. LTBI-DM participants had significantly decreased dual-functional (IFN-γ + IL-2 + , IFN-γ + TNF + and IL-2 + TNF + ) and mono-functional (IFN-γ + , IL-2 + and TNF + ) central and effector memory CD4 + responses compared to LTBI-only participants. Conclusion Type 2 DM impairs the memory phenotypes and functional profiles of Mtb -specific CD4 + and CD8 + T cells, potentially indicating underlying immunopathology towards increased active TB disease risk.
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2024.1480739
DOI:
10.3389/fimmu.2024.1480739.s001
DOI:
10.3389/fimmu.2024.1480739.s002
DOI:
10.3389/fimmu.2024.1480739.s003
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2024
detail.hit.zdb_id:
2606827-8
