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- Title
Impaired T-cell response to phytohemagglutinin (PHA) in tuberculosis patients is associated with high IL-6 plasma levels and normalizes early during anti-mycobacterial treatment.
- Authors
Vivekanandan, Monika M.; Adankwah, Ernest; Aniagyei, Wilfred; Acheampong, Isaac; Minadzi, Difery; Yeboah, Augustine; Arthur, Joseph F.; Lamptey, Millicent; Abass, Mohammed K.; Kumbel, Francis; Osei-Yeboah, Francis; Gawusu, Amidu; Debrah, Linda Batsa; Owusu, Dorcas O.; Debrah, Alexander; Mayatepek, Ertan; Seyfarth, Julia; Phillips, Richard O.; Jacobsen, Marc
- Abstract
Purpose: Human tuberculosis is characterized by immunopathology that affects T-cell phenotype and functions. Previous studies found impaired T-cell response to phytohemagglutinin (PHA) in patients with acute tuberculosis. However, the influence of disease severity, affected T-cell subsets, and underlying mechanisms remain elusive. Methods: Here we investigated PHA-induced and antigen-specific T-cell effector cytokines in tuberculosis patients (n = 55) as well as in healthy asymptomatic contacts (n = 32) from Ghana. Effects of Mycobacterium (M.) tuberculosis sputum burden and treatment response were analyzed and compared during follow-up. Finally, cytokine characteristics of the aberrant plasma milieu in tuberculosis were analyzed as a potential cause for impaired PHA response. Results: PHA-induced IFN-γ expression was significantly lower in sputum-positive tuberculosis patients as compared to both, contacts and paucibacillary cases, and efficiently discriminated the study groups. T-cell responses to PHA increased significantly early during treatment and this was more pronounced in tuberculosis patients with rapid treatment response. Analysis of alternative cytokines revealed distinct patterns and IL-22, as well as IL-10, showed comparable expression to IFN-γ in response to PHA. Finally, we found that high IL-6 plasma levels were strongly associated with impaired IFN-γ and IL-22 response to PHA. Conclusion: We conclude that impaired T-cell response to PHA stimulation in acute tuberculosis patients (i) was potentially caused by the aberrant plasma milieu, (ii) affected differentially polarized T-cell subsets, (iii) normalized early during treatment. This study shed light on the mechanisms of impaired T-cell functions in tuberculosis and yielded promising biomarker candidates for diagnosis and monitoring of treatment response.
- Subjects
INTERLEUKINS; PLANT proteins; TUBERCULOSIS; RESEARCH funding; DESCRIPTIVE statistics
- Publication
Infection, 2023, Vol 51, Issue 4, p1013
- ISSN
0300-8126
- Publication type
Article
- DOI
10.1007/s15010-023-01977-1