Pro-fibrinolytic potential of the third larval stage of Ascaris suum as a possible mechanism facilitating its migration through the host tissues

Abstract

Background: Ascaris roundworms are the parasitic nematodes responsible for causing human and porcine ascariasis. Whereas A. lumbricoides is the most common soil-transmitted helminth infecting humans in the world, A. suum causes important economic losses in the porcine industry. The latter has been proposed as a model for the study of A. lumbricoides since both species are closely related. The third larval stage of these parasites carries out an intriguing and complex hepatopulmonary route through the bloodstream of its hosts. This allows the interaction between larvae and the physiological mechanisms of the hosts circulatory system, such as the fibrinolytic system. Parasite migration has been widely linked to the activation of this system by pathogens that are able to bind plasminogen and enhance plasmin generation. Therefore, the aim of this study was to examine the interaction between the infective third larval stage of A. suum and the host fibrinolytic system as a model of the host-Ascaris spp. relationships. Methods: Infective larvae were obtained after incubating and hatching fertile eggs of A. suum in order to extract their cuticle and excretory/secretory antigens. The ability of both extracts to bind and activate plasminogen, as well as promote plasmin generation were assayed by ELISA and western blot. The location of plasminogen binding on the larval surface was revealed by immunofluorescence. The plasminogen-binding proteins from both antigenic extracts were revealed by two-dimensional electrophoresis and plasminogen-ligand blotting, and identified by mass spectrometry. Results: Cuticle and excretory/secretory antigens from infective larvae of A. suum were able to bind plasminogen and promote plasmin generation in the presence of plasminogen activators. Plasminogen binding was located on the larval surface. Twelve plasminogen-binding proteins were identified in both antigenic extracts. Conclusions: To the best of our knowledge, the present results showed for the first time, the pro-fibrinolytic potential of infective larvae of Ascaris spp., which suggests a novel parasite survival mechanism by facilitating the migration through host tissues.

Host-Parasite Relationships in Porcine Ascariosis: Anticoagulant Potential of the Third Larval Stage of Ascaris suum as a Possible Survival Mechanism

“…All these results are in line with those obtained in the previous study, which showed the pro-fibrinolytic potential of AsL3 [ 18 ]. The present work reinforces the idea that AsL3 could modulate the haemostatic system of their host for their own benefit, not only through the dissolution of blood clots, but also preventing their formation.…”

“…In a previous study, we have recently demonstrated the capacity of the cuticle and excretory/secretory antigenic extracts of AsL3 (AsL3C and AsL3ES) to activate the host fibrinolytic system, which represents the mechanism of the haemostatic system responsible for dissolving blood clots [ 18 ]. In order to complement this study and contribute to the knowledge of the host-parasite relationships in porcine ascariosis, the present work was carried out with the aim of evaluating the ability of AsL3C and AsL3ES to inhibit the coagulation cascade of the host as a potential survival mechanism.…”

Morphological variability in the mucosal attachment site ofTrichuris murisrevealed by X-ray microcomputed tomography

“…In a broader context, we have demonstrated how microCT offers an opportunity to reassess the life-cycles of other parasites, and characterize intra-tissue migration and establishment with additional clarity. For example, Ascaris is another soil transmitted helminth which migrates through the lungs and, and 3D imaging of the distribution of worm larvae may clarify preferential routes in this poorly-understood migration [42]. Likewise, flatworms of the genus Schistosoma migrate through skin and lungs, with chronic infection featuring egg-associated granulomas in the liver, intestine or bladder and other organs [43].…”

S-Methyl-(2-Methoxycarbonylamino-Benzimidazole-5) Thiosulfonate as a Potential Antiparasitic Agent—Its Action on the Development of Ascaris suum Eggs In Vitro

“…A. suum is often postulated as a model for research on human infection by Ascaris lumbricoides Linnaeus, 1758. Human ascariasis affects approximately 820 million people, most often the younger generations, especially in areas with poor access to water, sanitation and hygiene [ 2 , 3 , 4 , 5 ]. It is standard to use large-scale preventive chemotherapy to control for geohelminths due to the large epidemic threat [ 6 ].…”