Background:
Individuals with concurrent tuberculosis (TB) and Type 2 diabetes (DM) face a higher risk of adverse clinical outcomes. While heightened pro-inflammatory cytokines and defective phagocytosis have been observed in these patients, the profiles of lipid mediators — which are critical to both the inflammatory process and its resolution — have not yet been characterized by TB and TB-DM status. Understanding the molecular balance between pro-inflammatory (e.g., leukotrienes and prostaglandins) and specialized pro-resolving mediators (SPMs) is essential to delineate the immunopathology of this comorbidity.
Abstract:
Methods: A nested cross-sectional study was conducted with 40 treatment-naïve pulmonary TB patients (20 with newly diagnosed DM and 20 without DM) from a cohort in Pune, India. A total of 37 lipid mediators from four major bioactive metabolomes were quantified in serum samples using targeted lipid mediator profiling and correlation-based network analysis.
Results: The arachidonic acid-derived leukotrienes ($LTB_{4}$) and prostaglandins ($PGE_{2}$, $PGF_{2a}$) were the most abundant pro-inflammatory mediators, while lipoxins ($LXB_{4}$) and maresins (MCTR3) were the most abundant pro-resolving mediators in both groups. Network analysis revealed that individuals with TB-DM exhibited significantly higher connectivity and more coordinated responses between pro-inflammatory and pro-resolving mediators compared to those with TB alone ($P < 0.0001$).
Conclusion: TB-DM is characterized by a distinct molecular balance of lipid mediators. The increased connectivity suggests a more complex regulatory environment that potentially contributes to the pathogenesis and severity of the TB-DM comorbidity.
Keywords: Tuberculosis, Diabetes, lipids, inflammation, specialized pro-resolving mediators, prostaglandins, leukotrienes, lipoxins, resolvins
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- Data de Publicação: 08/11/2019
- Autores: Rupak Shivakoti, Jesmond Dalli, Dileep Kadam, Sanjay Gaikwad, Madhusudan Barthwal, Romain A. Colas, Francesca Mazzacuva, Rahul Lokhande, Sujata Dharmshale, Renu Bharadwaj, Anju Kagal, Neeta Pradhan, Sona Deshmukh, Sachin Atre, Tushar Sahasrabudhe, Arjun Kakrani, Vandana Kulkarni, Swapnil Raskar, Nishi Suryavanshi, Sandy Chon, Akshay Gupte, Amita Gupta, Nikhil Gupte, Mar ́ıa B. Arriaga, Kiyoshi F. Fukutani, Bruno B. Andrade, Jonathan E. Golub, Vidya Mave
