Altered Interferon Responses in Tuberculosis Patients with Type II Diabetes: Implications for Increased Disease Susceptibility
BACKGROUND: Individuals with type 2 diabetes are three times more likely to develop active tuberculosis (TB) after infection compared to those without diabetes. The mechanisms behind this increased risk remain unclear but may involve abnormal immune responses, including enhanced pro-inflammatory act...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | Journal of Global Antimicrobial Resistance |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213716524003527 |
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| author | Nofri Rahmadika Jackie M Cliff Ji Sook Lee |
| author_facet | Nofri Rahmadika Jackie M Cliff Ji Sook Lee |
| author_sort | Nofri Rahmadika |
| collection | DOAJ |
| description | BACKGROUND: Individuals with type 2 diabetes are three times more likely to develop active tuberculosis (TB) after infection compared to those without diabetes. The mechanisms behind this increased risk remain unclear but may involve abnormal immune responses, including enhanced pro-inflammatory activity and altered cell phenotypes, particularly involving type-1 and type-2 interferon responses. METHOD: This study used flow cytometry and ELISA to assess type-1 and type-2 interferon production in peripheral blood mononuclear cells (PBMCs) from healthy BCG-vaccinated donors exposed to live Mycobacterium bovis (BCG). The expression of six type-1 interferon-inducible genes was evaluated in PBMC and whole blood cultures using quantitative real-time RT-PCR. Additionally, plasma IFNα/γ levels in tuberculosis patients with and without type II diabetes (n = 120) were measured.Results revealed that IFN-α was undetectable in PBMCs cultured with BCG, although six IFN-α-responsive genes were notably upregulated. IFN-γ levels were significantly elevated in TB-only and TB-pre-DM patients, but not in those with both TB and diabetes. Plasma IFN-α levels remained consistently low across all patient groups, with no significant differences detected.These findings suggest that IFN-γ responses vary among TB patients depending on their diabetes status. IFN-α is not significantly upregulated in response to BCG stimulation in PBMCs. This highlights the complexity of the immune response in TB patients with type II diabetes and suggests a potential role of interferon pathways in their increased susceptibility to TB. |
| format | Article |
| id | doaj-art-653312cd831d449ba0e16ed6c22e0a7a |
| institution | DOAJ |
| issn | 2213-7165 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Global Antimicrobial Resistance |
| spelling | doaj-art-653312cd831d449ba0e16ed6c22e0a7a2025-08-20T02:57:24ZengElsevierJournal of Global Antimicrobial Resistance2213-71652024-12-01395510.1016/j.jgar.2024.10.175Altered Interferon Responses in Tuberculosis Patients with Type II Diabetes: Implications for Increased Disease SusceptibilityNofri Rahmadika0Jackie M Cliff1Ji Sook Lee2London School of Hygiene and Tropical Medicine (LSHTM),University of Indonesia, Andalas UniversityLondon School of Hygiene & Tropical Medicine (LSHMT). Brunel UniversityLondon School of Hygiene & Tropical Medicine (LSHMT). Brunel UniversityBACKGROUND: Individuals with type 2 diabetes are three times more likely to develop active tuberculosis (TB) after infection compared to those without diabetes. The mechanisms behind this increased risk remain unclear but may involve abnormal immune responses, including enhanced pro-inflammatory activity and altered cell phenotypes, particularly involving type-1 and type-2 interferon responses. METHOD: This study used flow cytometry and ELISA to assess type-1 and type-2 interferon production in peripheral blood mononuclear cells (PBMCs) from healthy BCG-vaccinated donors exposed to live Mycobacterium bovis (BCG). The expression of six type-1 interferon-inducible genes was evaluated in PBMC and whole blood cultures using quantitative real-time RT-PCR. Additionally, plasma IFNα/γ levels in tuberculosis patients with and without type II diabetes (n = 120) were measured.Results revealed that IFN-α was undetectable in PBMCs cultured with BCG, although six IFN-α-responsive genes were notably upregulated. IFN-γ levels were significantly elevated in TB-only and TB-pre-DM patients, but not in those with both TB and diabetes. Plasma IFN-α levels remained consistently low across all patient groups, with no significant differences detected.These findings suggest that IFN-γ responses vary among TB patients depending on their diabetes status. IFN-α is not significantly upregulated in response to BCG stimulation in PBMCs. This highlights the complexity of the immune response in TB patients with type II diabetes and suggests a potential role of interferon pathways in their increased susceptibility to TB.http://www.sciencedirect.com/science/article/pii/S2213716524003527Tuberculosistype-2 diabetes mellitustype-1 interferontype-2 interferonPBMCBCG |
| spellingShingle | Nofri Rahmadika Jackie M Cliff Ji Sook Lee Altered Interferon Responses in Tuberculosis Patients with Type II Diabetes: Implications for Increased Disease Susceptibility Journal of Global Antimicrobial Resistance Tuberculosis type-2 diabetes mellitus type-1 interferon type-2 interferon PBMC BCG |
| title | Altered Interferon Responses in Tuberculosis Patients with Type II Diabetes: Implications for Increased Disease Susceptibility |
| title_full | Altered Interferon Responses in Tuberculosis Patients with Type II Diabetes: Implications for Increased Disease Susceptibility |
| title_fullStr | Altered Interferon Responses in Tuberculosis Patients with Type II Diabetes: Implications for Increased Disease Susceptibility |
| title_full_unstemmed | Altered Interferon Responses in Tuberculosis Patients with Type II Diabetes: Implications for Increased Disease Susceptibility |
| title_short | Altered Interferon Responses in Tuberculosis Patients with Type II Diabetes: Implications for Increased Disease Susceptibility |
| title_sort | altered interferon responses in tuberculosis patients with type ii diabetes implications for increased disease susceptibility |
| topic | Tuberculosis type-2 diabetes mellitus type-1 interferon type-2 interferon PBMC BCG |
| url | http://www.sciencedirect.com/science/article/pii/S2213716524003527 |
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