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Decreasing immunogenicity of developing schistosome larvae
Abstract:
Cercariae, skin stage schistosomula, and lung stage schistosomula of Schistosoma mansoni were attenuated by gamma irradiation and tested for their ability to induce protective immunity against cercarial challenge in C57Bl/6J mice. The highest levels of resistance were induced by cercariae administered either percutaneously or intramuscularly. Skin stage schistosomula inoculated intramuscularly gave less protection while lung stage schistosomula from syngeneic donors were the least immunogenic. A similar ranking in immunogenicity was observed when the anti-skin stage schistosomular antibody responses induced by the different parasite stages were compared. In contrast, none of the immunization protocols were found to stimulate antibodies capable of recognizing lung stage schistosomula. These results suggest that, as schistosome larvae mature from the cercarial to the lung stage, they undergo a substantial loss in immunogenicity. This change may help explain the failure of older larvae to be immunologically destroyed in infected hosts.
Insights
Irradiated Schistosoma mansoni cercariae and skin-stage larvae induced significant protective immunity in mice. Lung-stage larvae were least immunogenic, suggesting a loss of immune recognition during parasite maturation.
Area of Science:
- Parasitology
- Immunology
- Infectious Diseases
Background:
- Schistosoma mansoni is a parasitic flatworm causing schistosomiasis.
- Understanding the immunogenicity of different larval stages is crucial for vaccine development.
Purpose of the Study:
- To evaluate the immunogenicity of gamma-irradiated Schistosoma mansoni cercariae, skin-stage schistosomula, and lung-stage schistosomula.
- To determine the protective immunity induced by these stages against cercarial challenge in mice.
Main Methods:
- Schistosoma mansoni larval stages (cercariae, skin-stage, lung-stage) were attenuated using gamma irradiation.
- Immunization of C57Bl/6J mice with attenuated larvae via percutaneous, intramuscular, or intravenous routes.
- Assessment of protective immunity through challenge with cercariae.
- Comparison of anti-skin stage schistosomular antibody responses.
Main Results:
- Intramuscular or percutaneous administration of cercariae induced the highest levels of protective immunity.
- Skin-stage schistosomula induced less protection, and lung-stage schistosomula were the least immunogenic.
- Antibody responses correlated with protection, with no antibodies recognizing lung-stage schistosomula.
Conclusions:
- Schistosome larvae undergo a significant loss of immunogenicity as they mature from cercariae to lung-stage larvae.
- This developmental change in immunogenicity may contribute to immune evasion in infected hosts.
- Targeting earlier larval stages may be more effective for inducing protective immunity against schistosomiasis.