Expansion of Pathogen-Specific T-Helper 1 and T-Helper 17 Cells in Pulmonary Tuberculosis With Coincident Type 2 Diabetes Mellitus
| Autor: | Rathinam Sridhar, M. S. Jawahar, Vaithilingam V. Banurekha, Subash Babu, Nathella Pavan Kumar, Thomas B. Nutman |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Tuberculosis Mycobacterium tuberculosis Major Articles and Brief Reports Immune system Antigen Humans Immunology and Allergy Medicine Tuberculosis Pulmonary biology business.industry Type 2 Diabetes Mellitus Middle Aged Th1 Cells biology.organism_classification medicine.disease Interleukin 10 Blood Infectious Diseases Diabetes Mellitus Type 2 Immunology Interleukin 12 Cytokines Th17 Cells Female Interleukin 17 business |
| Zdroj: | The Journal of Infectious Diseases. 208:739-748 |
| ISSN: | 1537-6613 0022-1899 |
| DOI: | 10.1093/infdis/jit241 |
| Popis: | The association between diabetes mellitus (DM) and tuberculosis and their synergistic role in causing human disease has been appreciated for a long time but has only lately become a major topic of clinical and fundamental research [1]. While tuberculosis continues to be a major disease burden in developing countries, the rise in prevalence of type 2 DM has been rapid and relentless, and the dual burden of diabetes and tuberculosis clearly represents a serious global public health concern [2]. There is growing evidence that DM is an important risk factor for developing active pulmonary tuberculosis [3]. Based on murine models and human studies, immunity to Mycobacterium tuberculosis requires T-helper 1 (Th1) responses and (to a lesser extent) T-helper 17 (Th17) responses [4, 5]. Thus, interleukin 12, interferon γ (IFN-γ), and tumor necrosis factor α (TNF–α; along with interleukin 17 [IL–17] and interleukin 23) all play important roles in the induction and maintenance of protective immune responses against tuberculous [6–11]. Furthermore, multifunctional T cells, defined by their ability to coexpress ≥2 cytokines, have also been associated with resistance to infection in animal models [12] and in some human studies [13, 14]. To study influence of DM on CD4+ T-cell responses in active pulmonary tuberculosis, we examined baseline, antigen–specific, and polyclonal induction of single-, double-, and triple-cytokine–producing cells of the Th1 and Th17 subsets in individuals with active tuberculosis and coincident DM and compared them to individuals with active tuberculosis without diabetes. We show that those with tuberculosis coincident with DM have elevated frequencies of single- and double-cytokine–producing CD4+ Th1 cells, as well as increased frequencies of Th17 subsets following mycobacterial antigen stimulation in comparison to individuals with tuberculosis and without DM. We also show that this expansion of Th1 and Th17 cells is associated with increased systemic (plasma) levels of Th1- and Th17-associated cytokines. Thus, our data demonstrate that diabetes is associated with a profound alteration in the CD4+ T-cell response to M. tuberculosis, which possibly contributes to increased severity and/or immune-mediated pathology in tuberculosis. |
| Databáze: | OpenAIRE |
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