Open AccessMiltefosine Efficiently Eliminates Leishmania major Amastigotes from Infected Murine Dendritic Cells without Altering Their Immune Functions
Author(s) -
Klaus Griewank,
Caroline Gazeau,
Andreas Eichhorn,
Esther von Stebut
Publication year - 2010
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.01014-09
Subject(s) - miltefosine , biology , immune system , leishmania , cutaneous leishmaniasis , immunology , antigen presentation , leishmania major , antigen , microbiology and biotechnology , leishmaniasis , visceral leishmaniasis , t cell , parasite hosting , world wide web , computer science
As a treatment for leishmaniasis, miltefosine exerts direct toxic effects on the parasites. Miltefosine also modulates immune cells such as macrophages, leading to parasite elimination via oxidative radicals. Dendritic cells (DC) are critical for initiation of protective immunity againstLeishmania through induction of Th1 immunity via interleukin 12 (IL-12). Here, we investigated the effects of miltefosine on DC inLeishmania major infections. When cocultured with miltefosine for 4 days, the majority ofin vitro -infected DC were free of parasites. Miltefosine treatment did not influence DC maturation (upregulation of major histocompatibility complex II [MHC II] or costimulatory molecules, e.g., CD40, CD54, and CD86) or significantly alter cytokine release (IL-12, tumor necrosis factor alpha [TNF-α], or IL-10). Further, miltefosine DC treatment did not alter antigen presentation, since unrestricted antigen-specific proliferation of CD4+ and CD8+ T cells was observed upon stimulation with miltefosine-treated, infected DC. In addition, miltefosine applicationin vivo did not lead to maturation/emigration of skin DC. DC NO− production, a mechanism used by phagocytes to rid themselves of intracellular parasites, was also unaltered upon miltefosine treatment. Our data confirm prior studies indicating that in contrast to, e.g., pentavalent antimonials, miltefosine functions independently of the immune system, mostly through direct toxicity against theLeishmania parasite.