title: IL-10 blocks the development of resistance to re-infection with Schistosoma mansoni.
abstract: 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.
authors.affiliation: Immunopathogensis Section, Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Marlyand, United States of America. mwilson@nimr.mrc.ac.uk
authors.forename: Mark S
authors.initials: MS
authors.lastname: Wilson
authors.forename: Allen W
authors.initials: AW
authors.lastname: Cheever
authors.forename: Sandra D
authors.initials: SD
authors.lastname: White
authors.forename: Robert W
authors.initials: RW
authors.lastname: Thompson
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Wynn
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology; D000909:Antibodies, Helminth / Q000097:blood / Q000276:immunology; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D005260:Female; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D011223:Praziquantel / Q000494:pharmacology; D012550:Schistosoma mansoni / Q000276:immunology* / Q000378:metabolism; D012555:Schistosomiasis mansoni / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D000871:Anthelmintics; D000909:Antibodies, Helminth; C556062:IL10 protein, mouse; D007074:Immunoglobulin G; D016753:Interleukin-10; D007073:Immunoglobulin E; D011223:Praziquantel