Factors affecting the acquisition of resistance against Schistosoma mansoni in the mouse. Evidence that the mechanisms which mediate resistance during early patent infections may lack immunological specificity

Abstract

SUMMARYMice infected with 25 to 35 unsexed Schistosoma mansoni cercariae became resistant to homologous challenge by 8 weeks, and the degree of resistance that was acquired correlated with the size of the worm burden and the tissue egg burden. Mice given 100 male or 100 female cercariae alone failed to become resistant even after 30–40 weeks of infection. When a super-infection of 100 male or 100–300 female cercariae was given to mice with 25 unsexed cercariae, the degree of resistance that was acquired was generally lower than in mice given 25 unsexed cercariae alone. In the super-infected mice there was no correlation between the size of the worm burden (mainly unpaired male or female worms) and the degree of acquired resistance. In mice super-infected with male worms there was an inverse correlation between the number of male worms and the number of eggs deposited in the liver and intestine by each mature worm pair. A positive correlation was, however, still found between the degree of acquired resistance and total tissue egg counts in mice super-infected with single sex cercariae. Mice injected intraperitoneally or subcutaneously with intact S. mansoni eggs failed to become resistant to S. mansoni challenge. Transfer of lymphoid cells or serum, separately or together, from heavily infected and demonstrably resistant donor mice to naive normal or T-cell deprived recipients failed to render the recipients resistant to S. mansoni challenge. The results indicate that resistance to re-infection in mice with recently patent S. mansoni infections is dependent on the number of S. mansoni eggs entrapped in the tissues, and that excessive numbers of unpaired S. mansoni male or female worms can inhibit the fecundity of established worm pairs. The apparent acquired resistance to S. mansoni that has been observed in this model system may be largely a consequence of non-specific factors interfering with normal patterns of challenge worm migration and maturation.

Studies on the development of anti‐schistosomular surface antibodies by mice exposed to irradiated cercariae, adults and/or eggs of 5. mansoni

“…The failure of both the single sex-infected and the egg-injected mice to develop significant resistance confirms earlier results (Dean et al 1978, Bickle et al 1979b, Harrison et al 1982 and again highlights the question as to whether chronically infected mice develop resistance by immunologically-specific mechanisms. It has been suggested that the resistance of chronically infected mice to challenge is due to the interference with the normal migration of challenge schistosomula as a consequence of the pathological disturbance associated with intravascular egg deposition (Wilson 1980, Harrison et al 1982, rather than to immunologically specific anti-schistosomula effector mechanisms. This conclusion seems to be consistent with the failure of certain groups of workers to demonstrate passive protection by either parabiosis or serum transfer (Dean, Bukowski & Clark 198 I , Harrison et al 1982) using the chronically-infected mouse, whereas resistance conferred by vaccination with irradiated cercariae is transferable by parabiosis (Dean et al 1981).…”

Preliminary study on sex-related inflammatory reactions in mice infected with Schistosoma mansoni

“…The protective effects of unisexual primary infections against a bisexual challenge infection have been analyzed in two animal models: the mouse and the monkey. Unisexual primary infections in mice induced lower levels of resistance against a schistosome challenge infection compared to bisexual ones (Bickle et al 1979;MotaSantos et al 1981;Harrison et al 1982;Moloney et al 1986). Moreover, no difference in the protective effect was observed between unisexual male and female primary infections (Bickle et al 1979).…”

Biochemical and Immunologic Predictors of Efficacy of Treatment or Reinfection Risk for Schistosoma Mansoni

“…In addition to the intensity of transmission, age < 14 5 and sexual immaturity in humans have been associated with increased reinfection with S. mansoni. [6][7][8] Male sex has also been associated with increased susceptibility and severity of schistosomiasis, both in laboratory animals, 9 and population studies conducted in endemic areas. 10 To study whether other host factors, such as immune responsiveness or nutritional status, might be related to treatment outcome, we conducted a prospective cohort study of 106 infected children.…”