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.

Surface layer proteins from virulent Clostridium difficile ribotypes exhibit signatures of positive selection with consequences for innate immune response

“…Given the role of IL-10 in the differentiation of regulatory T cells in suppressing inflammatory responses [42, 43], increased levels of IL-10 may act to impair clearance mechanisms late in inflammation, allowing the bacteria to persist in the gut. IL-10 has previously been shown to block resistance to pathogens [44] and can directly inhibit phagosome maturation [45]. This correlates with our observation that RT 027 and 078 SLPs do not enhance phagocytosis rates relative to RT 001, despite a heighted cytokine response.…”

IL-4 and IFN-γ induced by human immunodeficiency virus vaccine in a schistosome infection model

“…36 On the other hand, IL-10 appears to block development of resistance to re-infection with S. mansoni. 31 IL-10 is likely to play other important roles in the regulation of disease, and further studies are underway.…”

“…It is well known that schistosomiasis leads to the development and may play a role blocking development of resistance to reinfection. 31 To investigate the potential role of IL-10 in balancing Th1 and Th2 cells following HIV vaccination of schistosome-infected mice, we tested the expression of IL-10 in infected mice one week following the last immunization with the vaccine. Fresh spleen lymphocytes from mice were stimulated with antigen for 5 h and stained with surface antibodies.…”

Helminth Infections and Host Immune Regulation

“…Cytokine responsiveness has also been reported to be suppressed in Schistosoma haematobium-infected individuals in regard to IL-4, IL-5, and IFN-␥ production (102), while parasite-specific IL-10 positively correlates with egg positivity and infection intensity (209). In mouse models, IL-10 is pivotal in the suppression of potentially protective antischistosome responses (302). Evidence that helminth parasitic infection actively suppresses immune responses also comes from studies in which responses to parasite antigens increase after the drug-induced clearance of parasites.…”