Leishmania amazonensis-dendritic cell interactions in vitro and the priming of parasite-specific CD4+ T cells in vivo

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81 Scopus citations

Abstract

The progressive disease following Leishmania amazonensis infection in mice requires functional CD4+ T cells, which are primed to a disease-promoting phenotype during the infection. To understand how these pathogenic T cells are generated and the role of dendritic cells (DCs) in this process, we use DCs of susceptible BALB/c and resistant C3H/HeJ mice to examine parasite-DC interactions in vitro as well as the effector phenotype of T cells primed by parasite-exposed DCs in vivo. Our results demonstrate that amastigotes and metacyclics efficiently enter and activate DCs of both genetic backgrounds. Infection with amastigotes fails falls to induce CD40-depedent IL-12 production, but rather potentiates IL-4 production in BALB/c DCs. Upon transfer into syngeneic recipients, amastigote-exposed BALB/c DCs prime parasite-specific Th cells to produce significantly higher levels of IL-4 and IL-10 than their C3H/HeJ counterparts. Transfer studies with IL-4-/- DCs indicate that this enhanced Th2 priming seen in BALB/c mice is partially due to the IL-4 production by amastigote-carrying DCs. These results suggest that L. amazonensis amastigotes may condition DCs of a susceptible host to a state that favors activation of pathogenic CD4+ T cells, and thereby provide a new perspective on the pathogenesis of cutaneous leishmaniasis and protozoan parasite-host interactions in general.

Original languageEnglish (US)
Pages (from-to)4534-4542
Number of pages9
JournalJournal of Immunology
Volume167
Issue number8
DOIs
StatePublished - Oct 15 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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