Authors

Discussion

Schistosomiasis has a high rate of morbidity induced, mainly, by the granulomas’ formation  by eggs deposited in mammalian host tissues, being correlated with the viability of mature eggs. Schistosomiasis treatment relies only on praziquantel administration. However, due to praziquantel limitations, functional studies to elucidate parasite’s biology are needed to find alternative therapies. Studies suggest that protein kinases (PKs) have an essential role in Schistosoma mansoni development and survival. The PK SmFES is important in signal transduction pathways involved in larval transformation after penetration into hosts. SmRAF can influence the development and reproduction of S. mansoni. Therefore, this study aimed to investigate the functions of SmFES and SmRAF PKs in S. mansoni development and during mammalian infection establishment, using knockdown by RNA interference. Thus, mice were infected with schistosomula knocked-down for Smfes and Smraf. The number of eggs in the mice intestine was quantified and their maturation was evaluated. The square lobe of the liver was separated and stained for histological slides. The granulomas present on the slides were photographed under an inverted microscope, the area was measured using the Image J software and the granulomas were classified. Afterward, the number of granulomas was counted according to the tissue area. The development and reproductive system of adult worms recovered from mice infected with knocked-down schistosomula were analyzed by confocal microscopy. Mice inoculated with Smraf-knocked-down parasites presented a 23% reduction in the egg number recovered from the intestine, whereas the SmFES group showed 57% more immature eggs in this tissue. The liver from mice infected with Smfes-knocked-down parasites presented 166% more granulomatous lesions from the necrotic-exudative evolutionary phase than exudative-productive. Besides, granulomas from the SmFES group showed a 44.4% area reduction. Mice from the SmRAF group showed 6X more hepatic granulomas and 96% more granulomas in necrotic-exudative stage than in exudative-productive phase. On the other hand, in the analysis of recovered adult worm phenotypes under a confocal microscope, it was found that the females of the SmFES group showed a significant decrease in the ovarian area of ​​29.7% to the area of ​​the negative control group and of 19.3% to GFP. This study reveals that SmFES influences egg maturation and exudate components, which affects granuloma formation. Accordingly, SmFES should be explored as a target to assist schistosomiasis morbidity control. Lastly, SmRAF may participate in egg production and perhaps, consequently, in granulomatous lesions formation, so more studies should be conducted to elucidate its role.