Spatial localization of cathepsins: Implications in immune activation and resolution during infections

Abstract

Cathepsins were first described, as endolysosomal proteolytic enzymes in reference to the organelles where they degrade the bulk of endogenous and exogenous substrates in a slightly acidic environment. These substrates include pathogens internalized via endocytosis and/or marked for destruction by autophagy. However, the role of cathepsins during infection far exceeds that of direct digestion of the pathogen. Cathepsins have been extensively investigated in the context of tumour associated immune cells and chronic inflammation. Several cathepsin-dependent immune responses develop in the endocytic pathway while others take place in the cytosol, the nucleus, or in the extracellular space. In this review we highlight the spatial localization of cathepsins and their implications in immune activation and resolution pathways during infection.

Controlled and Synchronised Vascular Regeneration upon the Implantation of Iloprost- and Cationic Amphiphilic Drugs-Conjugated Tissue-Engineered Vascular Grafts into the Ovine Carotid Artery: A Proteomics-Empowered Study

“…In combination with active biosynthetic processes, evident by increased amounts of the proteins participating in the translation, protein folding and assembly, and energy metabolism, these molecular patterns testified to the synchronisation between PCL degradation and vascular regeneration. Further, TEVGs did not demonstrate any signs of the infection such as precipitation of complement components or neutrophil markers, instead showing informative signatures of chronic inflammation remodeling, namely structural lysosomal proteins (which are well-established macrophage markers) and cathepsins, known as lysosomal but not blood- or extracellular matrix-derived enzymes [ 62 , 63 , 64 ]. This type of remodeling has already been reported in several studies [ 19 , 65 , 66 , 67 , 68 ], as well as the rapid degradation of the polymer scaffolds in sheep as compared to rats [ 25 , 34 , 69 , 70 , 71 , 72 , 73 ].…”

Cleavage of Occludin by Cigarette Smoke-Elicited Cathepsin S Increases Permeability of Lung Epithelial Cells

“…Recent findings have evidenced the emerging roles of lysosomal cysteine cathepsins in lung pathophysiology (for review: [17,28,29]). Under particular physiological and pathophysiological settings, cysteine cathepsins may be secreted into the extracellular space [10]. Contrary to other related cysteine cathepsins, extracellular CatS remains stable and active in neutral or slightly alkaline environments [33,40], which corresponds to the mucosal pH of the inflamed airways of smokers [66].…”

“…Cysteine cathepsins are primarily lysosomal proteases. Nevertheless, they can be secreted and found in the pericellular environment as soluble enzymes or associated with cell surfaces [9,10]. Besides their conventional recycling tasks, cysteine cathepsins are involved in specialized biological roles including the maturation of some prohormones, apoptosis, and antigen presentation [11,12].…”

The Interplay of Glycosaminoglycans and Cysteine Cathepsins in Mucopolysaccharidosis

“…In addition to the dysregulation of their enzymatic activity, the extra-lysosomal localizations of cysteine cathepsins are usually related to pathological disorders [ 84 ]. Cysteine cathepsins have been identified as key proteases in a wide range of diseases including cancer, muscular dystrophy, hepatitis, rheumatoid arthritis, cardiovascular and bone diseases, lung diseases, immune system-related disorders, and neurodegenerative diseases, several of which are associated with chronic inflammation [ 5 ].…”