Isoniazid preventive therapy modulates Mycobacterium tuberculosis-specific T-cell responses in individuals with latent tuberculosis and type 2 diabetes

Isoniazid preventive therapy modulates Mycobacterium tuberculosis-specific T-cell responses in individuals with latent tuberculosis and type 2 diabetes

Abstract Diabetes mellitus (DM) is a significant contributor to tuberculosis (TB) incidence and poor treatment outcomes. This study explored the impact of isoniazid preventive therapy (IPT) on Mycobacterium tuberculosis (Mtb)-specific T-cell memory phenotypes and function among participants with lat...

Full description

Saved in:
Bibliographic Details
Main Authors: Phillip Ssekamatte, Diana Sitenda, Rose Nabatanzi, Marjorie Nakibuule, Davis Kibirige, Andrew Peter Kyazze, David Patrick Kateete, Bernard Ssentalo Bagaya, Obondo James Sande, Reinout van Crevel, Stephen Cose, Irene Andia Biraro
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
Subjects:
Latent TB infection
Diabetes
T cells
Isoniazid preventive treatment
Memory phenotypes
Functional profiles
Online Access:https://doi.org/10.1038/s41598-025-95386-z
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Diabetes mellitus (DM) is a significant contributor to tuberculosis (TB) incidence and poor treatment outcomes. This study explored the impact of isoniazid preventive therapy (IPT) on Mycobacterium tuberculosis (Mtb)-specific T-cell memory phenotypes and function among participants with latent TB infection and DM (LTBI-DM) at baseline and after 6 months of IPT; and compared the responses to healthy controls (HC). Peripheral blood mononuclear cells were stimulated with ESAT-6 and CFP-10 peptide pools to analyse CD4+ and CD8+ T-cell responses using flow cytometry. In LTBI-DM participants, effector memory CD4+ and CD8+ T cells were decreased post-IPT, suggesting a shift towards a less-activated state or differentiation into other subsets. CXCR5 expression on both CD4+ and CD8+ T cells was upregulated, while PD-1 expression was downregulated post-IPT, indicating reduced T-cell exhaustion and improved homing capabilities. Lastly, IL-17 A and IL-13 production in CD4+ and CD8+ T cells was increased post-IPT, respectively, which play a role in enhanced Mtb infection control. The post-IPT T-cell alterations were similar to normal HC levels. These findings suggest that IPT modulates and normalises specific T-cell memory phenotypes and functional responses in LTBI-DM participants, potentially contributing to improved long-term immunity and protection against TB. This study highlights the importance of preventive therapy in high-risk populations, and larger studies with more extended follow-up are needed to assess long-lasting IPT effects.
ISSN:2045-2322

Similar Items