IL-12 eliminates the Th-2 dependent protective immune response of mice to larval Strongyloides stercoralis.
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 beta 2-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-gamma 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.
Rotman
H L
HL
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Schnyder-Candrian
S
S
Scott
P
P
Nolan
T J
TJ
Schad
G A
GA
Abraham
D
D
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D047209:Eosinophil Peroxidase; D007109:Immunity / Q000187:drug effects; D007114:Immunization; D018664:Interleukin-12 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology; D007814:Larva / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010544:Peroxidases / Q000032:analysis; D017171:Strongyloides stercoralis / Q000276:immunology*; D013322:Strongyloidiasis / Q000276:immunology* / Q000517:prevention & control; D006377:T-Lymphocytes, Helper-Inducer; D018418:Th2 Cells / Q000276:immunology*
D015848:Interleukin-5; D018664:Interleukin-12; D015847:Interleukin-4; D047209:Eosinophil Peroxidase; D010544:Peroxidases