Date of Completion
lipopolysaccharide, LPS, noncanonical inflammasome, E. coli, caspase-11, infection, bacteria, virus, galectin-8, EMCV
Vijay A. K. Rathinam
Sivapriya Kailasan Vanaja
Robert B. Clark
Field of Study
Doctor of Philosophy
Bacterial and viral infections represent major health and economic burdens on the global population. In this study, we unravel the molecular mechanisms governing bacterial sepsis and picornavirus infections. Specifically, we delineate the structural determinants of the sepsis endotoxin LPS and provide evidence that the LPS core sugars are necessary for its cytosolic access and engagement with the noncanonical inflammasome. Mice injected with E. coli lacking LPS inner core exhibited diminished activation of inflammasome-dependent cytokines while normally activating LPS-induced TLR4 signaling. We also establish galectin-8, a member of the galectin family of proteins, as a critical component in the host defense against picornavirus infection. Mice lacking galectin-8 succumbed faster to encephalomyocarditis virus (EMCV) infection while wild-type mice were more resistant to the virus. Mechanistically, cells lacking galectin-8 displayed reduced autophagic flux and increased viral burdens during picornavirus infection, implicating galectin-8 in the autophagy-mediated degradation of EMCV. Our findings provide mechanistic insights into the molecular mechanisms underlying bacterial and viral infections in an effort to contribute to the development of effective therapeutic strategies against microbial pathogens.
Behl, Bharat, "Intracellular Host Defense in Microbial Infections" (2019). Doctoral Dissertations. 2208.
Available for download on Wednesday, May 22, 2024