"Glucose Transporter Expression in

Lung Granulomas from

Mycobacterium Tuberculosis-Infected Monkeys"

Abstract:  Tuberculosis (TB) remains a major threat to public health that causes tremendous morbidity and mortality in developing countries. The diagnostic tests for TB have problems with sensitivity, specificity, and ability to measure treatment outcomes. Positron emission tomography/computed tomography (PET/CT) imaging techniques can provide a fast and sensitive way of diagnosing active TB and can be a valuable tool of studying TB-associated inflammation in tissues. The most common PET probe is FDG, a glucose analog that is taken up by metabolically active cells, but the factors driving FDG uptake and the cells responsible for this in granulomas remain unknown. Our study focused on expression of glucose transporters (Gluts), a diverse set of proteins involved in glucose metabolism, in granulomas from Mycobacterium tuberculosis-infected monkeys. Our objective was to measure Glut expression, localization, and cellular source. We used RT-PCR and multi-color immunohistochemistry to accomplish this objective. We found that there was substantial variation in Glut expression between granulomas and uninfected lung, and that expression of individual Gluts did not correlate with FDG uptake in tissues. Our immunohistochemical studies demonstrated that Glut1 and 3 were strongly expressed by epithelioid macrophages, a cell type that exists in hypoxic environments and is likely to be using glycolysis to generate energy. We also identified a correlation between neutrophils and FDG uptake, suggesting these cells may contribute to PET/CT-measured inflammation in granulomas. Our results suggest that multiple factors, rather than a single Glut, drive FDG uptake in granulomas, but also indicate Glut expression on specific cell populations may strongly influence PET/CT detection of TB. Future work identifying the relationship between these cell populations and changes in FDG uptake over the course of disease may lead to important new information on pathogenesis in TB.