Biological roles of cysteine proteinases in the pathogenesis ofTrichomonas vaginalis

Abstract

Human trichomonosis, infection with Trichomonas vaginalis, is the most common non-viral sexually transmitted disease in the world. The host-parasite interaction and pathophysiological processes of trichomonosis remain incompletely understood. This review focuses on the advancements reached in the area of the pathogenesis of T. vaginalis, especially in the role of the cysteine proteinases. It highlights various approaches made in this field and lists a group of trichomonad cysteine proteinases involved in diverse processes such as invasion of the mucous layer, cytoadherence, cytotoxicity, cytoskeleton disruption of red blood cells, hemolysis, and evasion of the host immune response. A better understanding of the biological roles of cysteine proteinases in the pathogenesis of this parasite could be used in the identification of new chemotherapeutic targets. An additional advantage could be the development of a vaccine in order to reduce transmission of T. vaginalis.

Humoral and T cell–mediated immune response against trichomoniasis

“…Trichomonas vaginalis infection induces apoptosis and production of immunosuppressive cytokines (IL‐10, TGF‐β) . These properties are largely attributed to the CP30 activity, as this proteinase induces apoptosis in VECs and in several types of mucosal immune cells.…”

“…These properties are largely attributed to the CP30 activity, as this proteinase induces apoptosis in VECs and in several types of mucosal immune cells. T. vaginalis proteins, adhesins and CP30 induce caspase‐mediated apoptosis in T cells, macrophages and DCs along with the production of immunosuppressive cytokine response . CP30‐specific antibody decreases cytoadherence of T. vaginalis up to 50% .…”

Bulky Trichomonad Genomes: Encoding a Swiss Army Knife

“…Analysis of cysteine proteases from many parasitic protozoa has revealed the diverse role that cysteine proteases play, not only in host tissue destruction and nutrient acquisition but also in housekeeping tasks, encystation, excystation, host invasion, and other important pathogenic processes [74][75][76]. In trichomonads cysteine proteases are implicated in host protein degradation, haemolysis and nutrient acquisition, although also take part in other pathogenic processes such as adhesion [77,78].…”

“…foetus expresses cysteine proteases that cleave lactoferrin, liberating iron [83]. Similarly, T. vaginalis cysteine proteases degrade haemoglobin [77], liberated following the lysis of red blood cells by perforin like proteins [8]. T. vaginalis cysteine proteases also degrade IgG, IgM and IgA, fibronectin and various types of collagen [56,77].…”

“…Similarly, kinases also regulate signal transduction by controlling processes such as phagocytosis and motility; essential functions in the pathogenesis of amoebiasis [61,63,64]. Cysteine proteases are recognised as key virulence factors in pathogenic protozoa, facilitating the destruction of host tissues and the acquisition of nutrients [77,94]. Metabolic enzymes are not typically associated with virulence, though some T. vaginalis metabolic enzymes are regulated differently to their paralogues suggesting they are favoured under specific conditions or, that they may have acquired new functions [29,59].…”