IL-10 Blocks the Development of Resistance to Re-Infection with Schistosoma mansoni

PLoS Pathogens

Allen W. Cheever¹  Mark S. Wilson²  Thomas A. Wynn²  Sandra D. White²  Robert W. Thompson² 

[1] Biomedical Research Institute, Rockville, Maryland, United States of America;Immunopathogensis Section, Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Marlyand, United States of America

关键词: Immune response;    Enzyme-linked immunoassays;    Spleen;    Cytokines;    Lymph nodes;    Mouse models;    Parasitic diseases;    Schistosoma mansoni;   

DOI  :  10.1371/journal.ppat.1002171

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY