osteoprotegerin and Leishmaniasis--Cutaneous

Blockade of TNF-related activation-induced cytokine (TRANCE)-receptor activator of NF-kappaB (RANK) interaction reverses healing in CD40L(-/-) mice infected with Leishmania major. Although previous studies demonstrated a requirement for CD40-CD40L interaction in production of IL-12 and the development of resistance to Leishmania infection, we recently showed that CD40L(-/-) mice control infection when inoculated with low numbers of parasites and that cells from these mice produce IL-12. Here, we show that in vivo treatment with a TRANCE receptor fusion protein results in a decrease in numbers of IL-12 producing cells as well as a shift from a dominant Th1 to Th2 type response in infected mice. These results demonstrate that CD40L(-/-) mice use the TRANCE-RANK costimulatory pathway to promote IL-12 production and the activation of a protective Th1 type response.

Topics: Animals; Carrier Proteins; CD40 Ligand; Cells, Cultured; Down-Regulation; Female; Glycoproteins; Humans; Immunoglobulin Fc Fragments; Immunophenotyping; Interleukin-12; Leishmania major; Leishmaniasis, Cutaneous; Lymph Nodes; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Recombinant Fusion Proteins; Signal Transduction; Th1 Cells