The developing schistosome worms elicit distinct immune responses in different tissue regions
- Authors: McWilliam, Hamish , Driguez, Patrick , Piedrafita, David , Maupin, Kevin , Haab, Brian , McManus, Donald , Meeusen, Els
- Date: 2013
- Type: Text , Journal article
- Relation: Immunology and Cell Biology Vol. 91, no. 7 (2013), p. 477-485
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- Description: Schistosome parasites follow a complex migration path through various tissues, changing their antigenic profile as they develop. A thorough understanding of the antibody response in each tissue region could help unravel the complex immunology of these developing parasites and aid vaccine design. Here we used a novel strategy for analysing the local antibody responses induced by Schistosoma japonicum infection at each site of infection. Cells from rat lymph nodes draining the sites of larval migration (the skin and lungs), the liver-lymph nodes where adults reside and the spleens were cultured to allow the in vivo-induced antibody-secreting cells to release antibody into the media. The amount and isotype of antibodies secreted in the supernatants differed significantly in the different lymph nodes and spleen, corresponding with the migration path of the schistosome worms. In addition, there were significant differences in binding specificity, as determined by surface labelling, western blots and by screening a glycan array. Through capturing the local antibody response, this study has revealed dramatic differences in the quality and specificity of the immune response at different tissue sites, and highlighted the existence of stage-specific protein and carbohydrate antigens. This will provide a valuable tool for the isolation of novel vaccine targets against the larval stages of schistosomes.
Specific humoral response of hosts with variable schistosomiasis susceptibility
- Authors: Driguez, Patrick , McWilliam, Hamish , Gaze, Soraya , Piedrafita, David , Pearson, Mark , Nakajima, Rie , Duke, Mary , Trieu, Angela , Doolan, Denise , Cardoso, Fernanda , Jasinskas, Algis , Gobert, Geoffrey , Felgner, Philip , Loukas, Alex , Meeusen, Els , McManus, Donald
- Date: 2016
- Type: Text , Journal article
- Relation: Immunology and Cell Biology Vol. 94, no. 1 (2016), p. 52-65
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- Description: The schistosome blood flukes are some of the largest global causes of parasitic morbidity. Further study of the specific antibody response during schistosomiasis may yield the vaccines and diagnostics needed to combat this disease. Therefore, for the purposes of antigen discovery, sera and antibody-secreting cell (ASC) probes from semi-permissive rats and sera from susceptible mice were used to screen a schistosome protein microarray. Following Schistosoma japonicum infection, rats had reduced pathology, increased antibody responses and broader antigen recognition profiles compared with mice. With successive infections, rat global serological reactivity and the number of recognized antigens increased. The local antibody response in rat skin and lung, measured with ASC probes, increased after parasite migration and contributed antigen-specific antibodies to the multivalent serological response. In addition, the temporal variation of anti-parasite serum antibodies after infection and reinfection followed patterns that appear related to the antigen driving the response. Among the 29 antigens differentially recognized by the infected hosts were numerous known vaccine candidates, drug targets and several S. japonicum homologs of human schistosomiasis resistance markers - the tegument allergen-like proteins. From this set, we prioritized eight proteins that may prove to be novel schistosome vaccine and diagnostic antigens. © 2016 Australasian Society for Immunology Inc. All rights reserved.