IL-10 blocks the development of resistance to re-infection with Schistosoma mansoni.
Despite effective chemotherapy to treat schistosome infections, re-infection rates are extremely high. Resistance to reinfection can develop, however it typically takes several years following numerous rounds of treatment and re-infection, and often develops in only a small cohort of individuals. Us...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-08-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002171&type=printable |
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| author | Mark S Wilson Allen W Cheever Sandra D White Robert W Thompson Thomas A Wynn |
| author_facet | Mark S Wilson Allen W Cheever Sandra D White Robert W Thompson Thomas A Wynn |
| author_sort | Mark S Wilson |
| collection | DOAJ |
| description | Despite effective chemotherapy to treat schistosome infections, re-infection rates are extremely high. Resistance to reinfection can develop, however it typically takes several years following numerous rounds of treatment and re-infection, and often develops in only a small cohort of individuals. Using a well-established and highly permissive mouse model, we investigated whether immunoregulatory mechanisms influence the development of resistance. Following Praziquantel (PZQ) treatment of S. mansoni infected mice we observed a significant and mixed anti-worm response, characterized by Th1, Th2 and Th17 responses. Despite the elevated anti-worm response in PBMC's, liver, spleen and mesenteric lymph nodes, this did not confer any protection from a secondary challenge infection. Because a significant increase in IL-10-producing CD4(+)CD44(+)CD25(+)GITR(+) lymphocytes was observed, we hypothesised that IL-10 was obstructing the development of resistance. Blockade of IL-10 combined with PZQ treatment afforded a greater than 50% reduction in parasite establishment during reinfection, compared to PZQ treatment alone, indicating that IL-10 obstructs the development of acquired resistance. Markedly enhanced Th1, Th2 and Th17 responses, worm-specific IgG1, IgG2b and IgE and circulating eosinophils characterized the protection. This study demonstrates that blocking IL-10 signalling during PZQ treatment can facilitate the development of protective immunity and provide a highly effective strategy to protect against reinfection with S. mansoni. |
| format | Article |
| id | doaj-art-9053d5f2037340eaa4ba0f256bb8350e |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2011-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-9053d5f2037340eaa4ba0f256bb8350e2025-08-20T03:09:47ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742011-08-0178e100217110.1371/journal.ppat.1002171IL-10 blocks the development of resistance to re-infection with Schistosoma mansoni.Mark S WilsonAllen W CheeverSandra D WhiteRobert W ThompsonThomas A WynnDespite effective chemotherapy to treat schistosome infections, re-infection rates are extremely high. Resistance to reinfection can develop, however it typically takes several years following numerous rounds of treatment and re-infection, and often develops in only a small cohort of individuals. Using a well-established and highly permissive mouse model, we investigated whether immunoregulatory mechanisms influence the development of resistance. Following Praziquantel (PZQ) treatment of S. mansoni infected mice we observed a significant and mixed anti-worm response, characterized by Th1, Th2 and Th17 responses. Despite the elevated anti-worm response in PBMC's, liver, spleen and mesenteric lymph nodes, this did not confer any protection from a secondary challenge infection. Because a significant increase in IL-10-producing CD4(+)CD44(+)CD25(+)GITR(+) lymphocytes was observed, we hypothesised that IL-10 was obstructing the development of resistance. Blockade of IL-10 combined with PZQ treatment afforded a greater than 50% reduction in parasite establishment during reinfection, compared to PZQ treatment alone, indicating that IL-10 obstructs the development of acquired resistance. Markedly enhanced Th1, Th2 and Th17 responses, worm-specific IgG1, IgG2b and IgE and circulating eosinophils characterized the protection. This study demonstrates that blocking IL-10 signalling during PZQ treatment can facilitate the development of protective immunity and provide a highly effective strategy to protect against reinfection with S. mansoni.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002171&type=printable |
| spellingShingle | Mark S Wilson Allen W Cheever Sandra D White Robert W Thompson Thomas A Wynn IL-10 blocks the development of resistance to re-infection with Schistosoma mansoni. PLoS Pathogens |
| title | IL-10 blocks the development of resistance to re-infection with Schistosoma mansoni. |
| title_full | IL-10 blocks the development of resistance to re-infection with Schistosoma mansoni. |
| title_fullStr | IL-10 blocks the development of resistance to re-infection with Schistosoma mansoni. |
| title_full_unstemmed | IL-10 blocks the development of resistance to re-infection with Schistosoma mansoni. |
| title_short | IL-10 blocks the development of resistance to re-infection with Schistosoma mansoni. |
| title_sort | il 10 blocks the development of resistance to re infection with schistosoma mansoni |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002171&type=printable |
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