Persistent URL of this record https://hdl.handle.net/1887/136088
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Tuberculosis & type 2 diabetes
and DM using two approaches. Firstly, we identified and analyzed human macrophage subsets and studied the interactions between these human cells and a major pathogen, Mycobacterium tuberculosis (Mtb), and the specific metabolic changes involved using well-controlled in vitro systems. Next, we employed metabolomics to determine the impact of concurrent TB-DM on circulating metabolites in patient cohorts ex vivo. In this thesis we present evidence...Show moreDiabetes mellitus type 2 (DM) is a major risk factor for developing active tuberculosis (TB) disease, yet the causal mechanisms driving this association remain largely elusive. As the incidence of DM is rising, especially in TB endemic countries, it is important to identify the relevant immunological and metabolic processes that underlie TB-DM comorbidity, because such insights will facilitate optimal treatment, diagnosis and prevention. In this thesis, we have started to unravel key factors underlying the association between TB
and DM using two approaches. Firstly, we identified and analyzed human macrophage subsets and studied the interactions between these human cells and a major pathogen, Mycobacterium tuberculosis (Mtb), and the specific metabolic changes involved using well-controlled in vitro systems. Next, we employed metabolomics to determine the impact of concurrent TB-DM on circulating metabolites in patient cohorts ex vivo. In this thesis we present evidence derived from in vitro experiments and from ex vivo observational data which collectively suggest a pathogenic role of atherogenic lipid species during TB development.
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- All authors
- Vrieling, F.
- Supervisor
- Ottenhoff, T.H.M.
- Co-supervisor
- Joosten, S.A.
- Committee
- Rensen, P.C.N; Guigas, B.G.A.; Spaink, H.P.; Hoeben, R.C.; Shiri-Sverdlov, R.; Bossche, J. van den
- Qualification
- Doctor (dr.)
- Awarding Institution
- Faculty of Medicine, Leiden University Medical Center (LUMC) , Leiden University
- Date
- 2020-09-03
- ISBN (print)
- 9789463808743
Funding
- Sponsorship
- The conducted research was supported by the TANDEM (Tuberculosis and Diabetes Mellitus) Grant of the ECFP7 (European Union’s Seventh Framework Programme) under Grant Agreement No. 305279; and by TBVAC2020 Grant of EC HOR2020 (Grant Agreement No. 643381).