Abstract
Phagocytosis and autophagy in macrophages have been shown to be essential to both innate and adaptive immunity. Lysosomes are the main catabolic subcellular organelles responsible for degradation and recycling of both extracellular and intracellular material, which are the final steps in phagocytosis and autophagy. However, the molecular mechanisms underlying lysosomal functions after infection remain obscure. In this study, we conducted a quantitative proteomics analysis of the changes in constitution and glycosylation of proteins in lysosomes derived from murine RAW 264.7 macrophage cells treated with different types of pathogens comprising examples of bacteria (Listeria monocytogenes, L. m), DNA viruses (herpes simplex virus type-1, HSV-1) and RNA viruses (vesicular stomatitis virus, VSV). In total, 3,704 lysosome-related proteins and 300 potential glycosylation sites on 193 proteins were identified. Comparative analysis showed that the aforementioned pathogens induced distinct alterations in the proteome of the lysosome, which is closely associated with the immune functions of macrophages, such as toll-like receptor activation, inflammation and antigen-presentation. The most significant changes in proteins and fluctuations in glycosylation were also determined. Furthermore, Western blot analysis showed that the changes in expression of these proteins were undetectable at the whole cell level. Thus, our study provides unique insights into the function of lysosomes in macrophage activation and immune responses.
Highlights
Lysosomes are dynamic vacuolar organelles in which diverse enzymes degrade and recycle extracellular and intracellular materials in an acidic environment
Our results provide evidences indicating that distinct events take place in the lysosomal compartment of macrophages according to the type of stimulation, and suggest that lysosomes may play a role in the signaling pathways involved in both innate and adaptive immune responses
We revealed that the changes in the lysosomal proteome varied according to the type of pathogens, and were closely related to the immune functions of macrophages
Summary
Lysosomes are dynamic vacuolar organelles in which diverse enzymes degrade and recycle extracellular and intracellular materials in an acidic environment. Regarding the adaptive immune system, lysosomal proteolysis generates peptides that bind major histocompatibility complex (MHC) molecules to present crucial information of pathogens for the surveillance by the diverse antigen receptors of the T lymphocyte system [7]. As macrophages change their functions in response to local micro-environmental signals, the roles of lysosomes in these different responses need to be elucidated
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