Search

The schistosome oviposition and granuloma constitution in the peritoneal cavity of AKR/J mice were evaluated. Groups of mice intraperitoneally infected with cercariae of Schistosoma mansoni were weekly euthanized during the acute (56 to 84 days post-infection (DPI)) and chronic (147 to 175 DPI) phase of infection. Schistosome developmental stages obtained via peritoneal lavage and perfusion of the portal system were inspected, counted and fixed, and peritoneal granulomata were then processed for histology. The morphological characterization and quantitative analysis of peritoneal schistosome eggs and granulomata were for the first time performed, such as the demonstration of the viability of miracidia obtained there from. Eutopic and ectopic mature schistosomes and normal pattern of worm oviposition were observed in all periods studied. However, the size of schistosome eggs from peritoneal cavity was smaller than observed for eggs laid by female worms from the portal system. The numbers of S. mansoni eggs and/or granulomata recovered from the peritoneal cavity was higher in chronic than acute infection, while the mean diameter of peritoneal chronic granulomata was smaller than for peritoneal acute granulomata. The constitution and evolution of these cellular reactions at histology were similar to that of hepatic granuloma, and peritoneal granulomata were subject to the host immunomodulation. In addition to the standardization of this experimental approach, which allows the obtaining of free schistosomal granulomata from peritoneal cavity of AKR/J mice, the potential use of these granulomata in ex vivo and in vivo studies is discussed.

Morphometric analysis of Schistosoma mansoni male worms obtained from AKR/J and Swiss mice was carried out. Rodents infected by the intraperitoneal route with 80 cercariae of the schistosome (LE strain) were killed by cervical dislocation at 45 and 60 days post-infection and both peritoneal lavage and perfusion of the portal system were performed for the recovery of adult worms. Characteristics including total body length, the distance between oral and ventral suckers, extension of testicular mass and the number of testes were considered in the morphological analysis. Changes that occurred in S. mansoni recovered from the peritoneal cavity or from the portal system of AKR/J and Swiss mice included total body length and reproductive characteristics. Significant morphometric alterations were also observed when worms recovered from the portal system of both strains of mice were compared with the schistosomes obtained from hamsters (Mesocricetus auratus), the vertebrate host in which the LE strain had been adapted and maintained by successive passages for more than four decades. The present results reinforce the idea that S. mansoni has high plastic potential and adaptive capacity.

The short-term effects of pentoxifylline (PTX) on granulomatous lesions during Schistosoma mansoni infection in Swiss mice were evaluated. Drug administration was initiated 42 and 140 days post-infection (DPI) for the acute and chronic infection groups, respectively. Treatment was carried out daily with 200 mg/kg (subcutaneous route) of the drug for five consecutive days. Recovery of parasites and tissues was performed at 49 DPI and 147 DPI, respectively. Liver histological analysis showed a decrease in the inflammatory reaction and fibrous content of the granulomas studied, and a significant reduction (P < 0.001) in their mean diameter was observed in the groups of rodents treated with PTX in acute and chronic infection, when compared to their respective control groups. However, no alteration in the number of S. mansoni recovered from the portal system was observed, and egg-laying kinetics was not notably modified by PTX treatment, and the immature stage distribution of S. mansoni eggs showed minor intrinsic variations with no statistical differences in the parameter second-stage/female/g among untreated mice and treated mice in acute and chronic infections, respectively, when evaluated by intestinal oograms. Data obtained indicate probable immunomodulatory effects of PTX in murine schistosomiasis both in acute and chronic infection.

The protection against Schistosoma mansoni infection was evaluated in SWISS mice orally vaccinated with an attenuated strain of Salmonella carrying a Sm14-based DNA vaccine. Although this formulation was not able to afford a reduction in the worm burden, a non-antigen-specific decrease in schistosome-induced granulomatous reaction was verified in livers of mice that received Salmonella.

Background: Schistosomiasis continues to be a significant public health problem. This disease affects 200 million people worldwide and almost 800 million people are at risk of acquiring the infection. Although vaccine development against this disease has experienced more failures than successes, encouraging results have recently been obtained using membrane-spanning protein antigens from the tegument of Schistosoma mansoni. Our group recently identified Sm29, another antigen that is present at the adult worm tegument surface. In this study, we investigated murine cellular immune responses to recombinant (r) Sm29 and tested this protein as a vaccine candidate., Methods and Findings: We first show that Sm29 is located on the surface of adult worms and lung-stage schistosomula through confocal microscopy. Next, immunization of mice with rSm29 engendered 51%, 60% and 50% reduction in adult worm burdens, in intestinal eggs and in liver granuloma counts, respectively (p<0.05). Protective immunity in mice was associated with high titers of specific anti-Sm29 IgG1 and IgG2a and elevated production of IFN-gamma, TNF-alpha and IL-12, a typical Th1 response. Gene expression analysis of worms recovered from rSm29 vaccinated mice relative to worms from control mice revealed a significant (q<0.01) down-regulation of 495 genes and up-regulation of only 22 genes. Among down-regulated genes, many of them encode surface antigens and proteins associated with immune signals, suggesting that under immune attack schistosomes reduce the expression of critical surface proteins., Conclusion: This study demonstrates that Sm29 surface protein is a new vaccine candidate against schistosomiasis and suggests that Sm29 vaccination associated with other protective critical surface antigens is the next logical strategy for improving protection.