RESUMEN
The rhesus macaque provides a unique model of acquired immunity against schistosomes, which afflict >200 million people worldwide. By monitoring bloodstream levels of parasite-gut-derived antigen, we show that from week 10 onwards an established infection with Schistosoma mansoni is cleared in an exponential manner, eliciting resistance to reinfection. Secondary challenge at week 42 demonstrates that protection is strong in all animals and complete in some. Antibody profiles suggest that antigens mediating protection are the released products of developing schistosomula. In culture they are killed by addition of rhesus plasma, collected from week 8 post-infection onwards, and even more efficiently with post-challenge plasma. Furthermore, cultured schistosomula lose chromatin activating marks at the transcription start site of genes related to worm development and show decreased expression of genes related to lysosomes and lytic vacuoles involved with autophagy. Overall, our results indicate that enhanced antibody responses against the challenge migrating larvae mediate the naturally acquired protective immunity and will inform the route to an effective vaccine.
Asunto(s)
Schistosoma mansoni/fisiología , Esquistosomiasis mansoni/inmunología , Animales , Anticuerpos Antihelmínticos/inmunología , Anticuerpos Antihelmínticos/farmacología , Antígenos Helmínticos/inmunología , Modelos Animales de Enfermedad , Epigénesis Genética/efectos de los fármacos , Femenino , Genes de Helminto/genética , Granulocitos/inmunología , Histonas/metabolismo , Interacciones Huésped-Parásitos/inmunología , Larva/efectos de los fármacos , Larva/genética , Larva/crecimiento & desarrollo , Linfocitos/inmunología , Macaca mulatta/inmunología , Macaca mulatta/parasitología , Masculino , Recuento de Huevos de Parásitos , Reinfección/inmunología , Esquistosomiasis mansoni/parasitologíaRESUMEN
The rhesus macaque provides a unique model of acquired immunity against schistosomes, which afflict >200 million people worldwide. By monitoring bloodstream levels of parasite-gut-derived antigen, we show that from week 10 onwards an established infection with Schistosoma mansoni is cleared in an exponential manner, eliciting resistance to reinfection. Secondary challenge at week 42 demonstrates that protection is strong in all animals and complete in some. Antibody profiles suggest that antigens mediating protection are the released products of developing schistosomula. In culture they are killed by addition of rhesus plasma, collected from week 8 post-infection onwards, and even more efficiently with post-challenge plasma. Furthermore, cultured schistosomula lose chromatin activating marks at the transcription start site of genes related to worm development and show decreased expression of genes related to lysosomes and lytic vacuoles involved with autophagy. Overall, our results indicate that enhanced antibody responses against the challenge migrating larvae mediate the naturally acquired protective immunity and will inform the route to an effective vaccine.
RESUMEN
Cyathostomins comprise around 50 parasite species of equids, offering a great challenge regarding their individual identification. The objective of our work was to improve identification of infective third stage larvae (L3) with a morphological key supplemented with detailed scientific illustrations based on our research and available literature. The highlighted features were; the number, arrangement, and shape of intestinal cells (IC), general features and the total body length of the eight different Cyathostomin sensu latum types (Type A, B, C, D, E, F, G, H), Gyalocephalus capitatus, and Posteriostomum spp. Due to variability, we were unable to define final body length measurements to differentiate L3 of cyathostomins. However, IC characteristics displayed a higher difference between L3 types than total body length. Through the number and arrangement of IC, 14 species were classified within three larval types. The classification of L3 into distinct larval types sensu latum gives us the advantage of reducing the number of probable species presented in equine faecal samples using a low-cost technique when monitoring the parasite fauna present in individual horses or on the farm level. The present improved identification key shall increase the diagnostic capabilities of classical equine parasitology techniques, using general L3 morphology thereby pragmatically improving regional and transnational epidemiological and biodiversity studies. The present key may also assist in defining the cyathostomin community in cyathostominosis clinical cases and within drug resistant populations across different management systems and geographical locations.
