title: Leishmania-macrophage interactions: insights into the redox biology.
abstract: Leishmaniasis is a neglected tropical disease that affects about 350 million individuals worldwide. The protozoan parasite has a relatively simple life cycle with two principal stages: the flagellated mobile promastigote living in the gut of the sandfly vector and the intracellular amastigote within phagolysosomal vesicles of the vertebrate host macrophage. This review presents a state-of-the-art overview of the redox biology at the parasite-macrophage interface. Although Leishmania species are susceptible in vitro to exogenous superoxide radical, hydrogen peroxide, nitric oxide, and peroxynitrite, they manage to survive the endogenous oxidative burst during phagocytosis and the subsequent elevated nitric oxide production in the macrophage. The parasite adopts various defense mechanisms to cope with oxidative stress: the lipophosphoglycan membrane decreases superoxide radical production by inhibiting NADPH oxidase assembly and the parasite also protects itself by expressing antioxidant enzymes and proteins. Some of these enzymes could be considered potential drug targets because they are not expressed in mammals. In respect to antileishmanial therapy, the effects of current drugs on parasite-macrophage redox biology and its involvement in the development of drug resistance and treatment failure are presented.
authors.affiliation: Laboratory of Microbiology Parasitology, and Hygiene, University of Antwerp, B-2020 Antwerp, Belgium.
authors.forename: Tim
authors.initials: T
authors.lastname: Van Assche
authors.forename: Maartje
authors.initials: M
authors.lastname: Deschacht
authors.forename: Raquel A Inocêncio
authors.initials: RA
authors.lastname: da Luz
authors.forename: Louis
authors.initials: L
authors.lastname: Maes
authors.forename: Paul
authors.initials: P
authors.lastname: Cos
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology; D007891:Leishmania / Q000187:drug effects / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D017382:Reactive Oxygen Species