Inhibiting the glycolysis rate-limiting enzyme PFKFB3 alters neutrophil interactions with Mycobacterium tuberculosis
Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B589
Abstract ID: 5425
Presenting Author:
Daniel S Lane , Graduate Student Researcher at Univ. of Pittsburgh Sch. of Pub. Hlth., Univ. of Pittsburgh
Abstract:
Tuberculosis (TB) is the leading cause of infectious disease-related mortality globally. TB is caused by Mycobacterium tuberculosis (Mtb) which infects myeloid cells and leads to formation of multicellular lesions called granulomas. Neutrophils are one of the earliest and most abundant cell types to respond to Mtb infection but neutrophilic recruitment and inflammation are linked to worse outcomes in TB. The basis for this is not clear but limiting neutrophil recruitment in TB has been suggested as an approach for improving outcomes in TB. Immunometabolism is a driver of immune function and may be a determinant of neutrophil function in TB represents a target for host-directed therapies for this disease. We targeted glycolysis at two different points, fatty acid oxidation, and oxidative phosphorylation to evaluate the role of these pathways in neutrophil function using phagocytosis of Mtb as a primary outcome measure. We found that perturbing glycolysis by inhibiting the rate-limiting enzyme PFKFB3 reduced phagocytosis of Mtb, while disrupting glycolysis with the glucose analog 2DG, did not. PFKFB3-inhibited neutrophils had higher expression of the glucose transporter GLUT1 and took up more glucose compared to other metabolically perturbed cells. These results indicate that metabolic pathways can be targeted to affect neutrophil interactions with Mtb and suggest that targeting different points in a metabolic pathway can differentially affect neutrophil function.
Inhibiting the glycolysis rate-limiting enzyme PFKFB3 alters neutrophil interactions with Mycobacterium tuberculosis
Category
Poster and Podium (Block Symposium)