LYSOSOME REMODELLING IN MACROPHAGES AFTER STIMULATION OF PATTERN RECOGNITION RECEPTORS

Candidate: Nemanja Ilic
Supervisor: Dr. Roberto Botelho

ABSTRACT

Pattern recognition receptors (PRRs) are critical in innate immunity. PRRs bind to conserved microbe-associatedmolecular patterns (MAMPs) to initiate an immune response. Previously shown in the PRR Toll-like receptor family (TLRs), TLR4-lipopolysaccharide stimulation mediated lysosomal remodelling in immune cells through the mechanistic target of rapamycin (mTOR) signalling hub. Lysosomes adapted an expanded tubular network, improving functions. Limited information is available on other PRRs/TLRs mediating lysosome remodelling. As PRRs share signalling pathways, we suspected signalling through other PRRs/TLRs could induce lysosome remodelling. To test this, we stimulated PRRs/TLRs in macrophages. Following stimulation, we imaged lysosomes through confocal microscopy to quantify lysosome remodelling. Here, we showed plasma membrane and endosomal TLR-mediated lysosome remodelling and their interactions with the mTOR pathway. We also show that other PRRs may promote lysosome tubulation. Overall, PRR-mediated lysosome remodelling may be associated with phagosome maturation as adaptations such as expansion may allow phagocytes engulfment of more material.

https://torontomu.zoom.us/j/97770765719?pwd=NnJkZ244TWpsQk1memJTQXdJSVUwUT09 (external link) 

Meeting ID: 977 7076 5719
Passcode: 682060