IL-12 eliminates the Th-2 dependent protective immune response of mice to larval Strongyloides stercoralis |
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Authors: | HL ROTMAN S SCHNYDER-CANDRIAN P SCOTT TJ NOLAN GA SCHAD & D ABRAHAM |
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Institution: | Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA; Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA |
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Abstract: | The goal of the present study was to determine if immune-mediated killing of S. stercoralis L3 in mice could be modulated by shifting from a Th-2 to a Th-1 type immune response. L3 killing in immunized mice was ablated in CD4+ T cell-depleted animals, but not in CD8+ T cell-depleted or β2-microglobulin-deficient mice. Treatment of immunized mice with IL-4 or IL-5 neutralizing MoAb significantly reduced the protective effects of vaccination against S. stercoralis , while protective immunity was unimpaired in IFN-γ knockout mice. Recombinant IL-12 was administered to infected mice to switch the immune response from a Th-2 to a Th-1 type response. Protective immunity was ablated in immunized mice that received IL-12 therapy. Eosinophil numbers, eosinophil peroxidase levels, and parasite-specific IgG1 levels were lowered in IL-12 treated immunized animals, and parasite-specific IgG2a levels were increased in these animals. The data indicate that eosinophils are important as mediators of larval killing, and that the establishment of Th-2 type immunity results in killing of infective S. stercoralis L3, while a shift to Th-1 type immunity abrogates protective responses. |
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Keywords: | IL-12 Strongyloides stercoralis nematode Th-2 immunity |
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