Affiliation:
1. Department of Dermatology, Johannes Gutenberg-University Mainz, Mainz, Germany
Abstract
ABSTRACT
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 against
Leishmania
through induction of Th1 immunity via interleukin 12 (IL-12). Here, we investigated the effects of miltefosine on DC in
Leishmania major
infections. When cocultured with miltefosine for 4 days, the majority of
in 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 application
in 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 the
Leishmania
parasite.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
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