Host-parasite interaction: parasite-derived and -induced proteases that degrade human extracellular matrix

Abstract

Parasitic protozoa are among the most important pathogens worldwide. Diseases such as malaria, leishmaniasis, amoebiasis, giardiasis, trichomoniasis, and trypanosomiasis affect millions of people. Humans are constantly threatened by infections caused by these pathogens. Parasites engage a plethora of surface and secreted molecules to attach to and enter mammalian cells. The secretion of lytic enzymes by parasites into host organs mediates critical interactions because of the invasion and destruction of interstitial tissues, enabling parasite migration to other sites within the hosts. Extracellular matrix is a complex, cross-linked structure that holds cells together in an organized assembly and that forms the basement membrane lining (basal lamina). The extracellular matrix represents a major barrier to parasites. Therefore, the evolution of mechanisms for connective-tissue degradation may be of great importance for parasite survival. Recent advances have been achieved in our understanding of the biochemistry and molecular biology of proteases from parasitic protozoa. The focus of this paper is to discuss the role of protozoan parasitic proteases in the degradation of host ECM proteins and the participation of these molecules as virulence factors. We divide the paper into two sections, extracellular and intracellular protozoa.

Figure 1

Extracellular parasite proteases. CPs: cysteine proteases, pink scissors; SPs: serine proteases, green scissors; MMPs: matrix metalloproteases, blue scissors; ECM extracellular matrix; EDG: electron-dense granules; POP: prolyl oligopeptidase; PAA: plasminogen activator activity; CatB: cathepsin B.

Figure 2

Intracellular parasite proteases. CPs: cysteine proteases, pink scissors; SPs: serine proteases, green scissors; MMPs: matrix metalloproteases, blue scissors; ECM extracellular matrix; POP: prolyl oligopeptidase; CatB: cathepsin B; MMC: migratory molecular complex; ROS: reactive oxygen species.