Browsing by Author "Klazen, Jessica"
Now showing 1 - 1 of 1
Results Per Page
Sort Options
- ItemInvestigating the role of immune-endocrine alterations during type 2 diabetes associated with changes in Mycobacterium tuberculosis growth(Stellenbosch : Stellenbosch University, 2017-03) Klazen, Jessica; Ronacher, K.; Kleynhans, L.; Stellenbosch University. Faculty of Medicine Health Sciences. Dept. of Biomedical Sciences: Molecular Biology and Human Genetics.Background There is a high co-prevalence between type 2 diabetes (DM2) and other infectious diseases. This is particularly problematic with the rise in co-prevalence between DM2 and Tuberculosis (TB). However, the underlying association between TB and DM2 is still poorly understood. We hypothesize that immune-endocrine alterations in latently infected individuals with DM2 are associated with reduced Mycobacterium tuberculosis (Mtb)-killing efficacy. We aimed to determine whether Mtb phagocytosis and/or killing efficacy of peripheral blood mononuclear cells (PBMCs) and monocytes (MNs) from close contacts (CCs) of TB patients with or without DM2 is altered and its association with physiological changes characteristic of DM2. In addition, we aimed to identify immune modulatory properties of endogenous hormones such as cortisol, leptin and insulin on PBMCs and MNs of latently infected individuals. Materials and methods First, we compared the bacterial burden in PBMCs and MNs of TB close contacts with normal to poorly controlled glycemia during an Mtb infection. We investigated the association between glycemic control, cells counts and hormone signatures, with bacterial burden in DM2 patients. Secondly, we treated PBMCs and MNs with cortisol, leptin and insulin to determine whether these hormones influenced bacterial burden, mycobacterium induced cytokine production and phenotypes of CD4+ and CD8+ T cells. Results Bacterial burden was increased in DM2 patients when compared to healthy participants in both PBMCs and MNs. High bacterial burden was associated poor glycemic control. DM2 patients had higher levels of neutrophil counts, white cell counts (WCC) and lymphocyte counts, but low percentage MNs in whole blood compared to healthy participants. Cortisol levels remained unchanged between the groups, however, there was a negative correlation between cortisol and interferon-γ (IFN-γ) (p=0.03, r=0.52) in the DM2 group. Cortisol, leptin and insulin did not influence the bacterial burden in both PBMCs and MNs. However, the hormones influenced the Mtb induced cytokine production in PBMCs. Cortisol decreased the production of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, TNF-β, IL-8, IFN-γ and granulocyte-macrophage colony stimulating factor (GM-CSF). Leptin decreased the production of IL-1RA, IL-13, IL-5, fibroblast growth factor (FGF)-2. Insulin decreased the production of vascular endothelial growth factor (VEGF), IL-1RA and increased the production of IL-5. Conclusion In DM2, phagocytosis and killing efficacy of PBMCs and MNs from CC of TB patients were associated with physiological changes characteristic to DM2. Poor bacterial control in DM2 was associated with hyperglycemia, chronic inflammation induced by increased WCC, neutrophil, and lymphocyte counts. The level of cortisol in DM2 individuals negatively correlated with IFN-γ, thus suppressing Th1 response. Furthermore, the study indicate that endogenous hormones such as cortisol, leptin and insulin could potentially mediate some cytokine response in DM2 patients. Cortisol potentially suppress macrophage activation or Th1 activity, which could lead to poor bacterial control. Whereas, leptin upregulates Th1 response that may improve bacterial control. However, its role still remains undetermined. The role of insulin is debatable as it may either induce a Th2 response, which could lead to poor bacterial control, or may a play a role in preventing the spread of Mtb to other organs by decreasing the production of VEGF. Therefore, during DM2, immune alterations and hyperglycemia are associated with decreased bacterial control, and that endocrine factors such as cortisol would suppress Th1 response, regardless whether it is elevated or not. Thus, would potentially exacerbate bacterial control in cases where DM2 is worsened by other complications.