The developing schistosome worms elicit distinct immune responses in different tissue regions

Abstract

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.

Local Antiglycan Antibody Responses to Skin Stage and Migratory Schistosomula of Schistosoma japonicum

“…Axillary and inguinal lymph nodes (LN) (skin LN) and mediastinal LN (lung LN) were isolated from an uninfected control group and from two groups of rats at 5 and 9 days after secondary infection, respectively. The timing of the isolation of LN corresponded to the expected peak in antibody production in the skin (5 days postinfection) and lung (9 days postinfection) LN (10). The LN were dissected, and cell suspensions were made and cultured at 37°C and 5% CO 2 for 5 days.…”

“…ASC probes were produced as described previously (10). In short, a Chinese strain of Oncomelania hupensis snails (Anhui Province, People's Republic of China) was used to obtain S. japonicum cercariae, which were subsequently used for the infection of female Wistar rats.…”

“…At the molecular level, the expression of proteins and glycans is developmentally regulated and subject to constant change during schistosome development (8,9). This specific antigen expression by different developmental stages could be a strategy to escape the host's immune system, but it may also lead to specific local protective immune responses of the host (10).…”

“…Therefore, the rat is a good model to study protective immune responses. Using this method, it was shown previously that migrating S. japonicum schistosomula in rats induced antibodies in the lung to several high-molecular-weight protein antigens of larvae and worms, as well as antibodies to synthetic glycan elements, including GlcNAc, LeX, and LacNAc and fucosylated N-glycan core structures (10,33). While the use of these nonspecific synthetic glycans provided insights into the potential importance of antiglycan antibodies, the naturally occurring glycans on the surfaces and in secretions of schistosomula are far more complex than the glycans previously studied and often carry glycan motifs unique to the schistosome.…”

Identification of Antigenic Glycans from Schistosoma mansoni by Using a Shotgun Egg Glycan Microarray

“…Recent studies have shown that a major part of the host immune response to infection is directed against carbohydrate (glycan) antigens in glycoproteins and glycolipids (10)(11)(12)(13)(14)(15)(16)(17). A wide variety of unusual antigenic determinants include glycans containing the LDN, fucosylated LDN sequences (LDNF, LDN-dF, FLDN, and FLDNF), Lewis X (Le x ), poly-Le x , core ␣3 fucose, and core ␤2 xylose structures ( Fig.…”