Leishmania donovani : Inhibition of phagosomal maturation is rescued by nitric oxide in macrophages

• Leishmania donovani promastigotes, the causative agent of visceral leishmaniasis, survive inside macrophages by inhibiting phagosomal maturation. The main surface glycoconjugate on promastigotes, lipophosphoglycan (LPG), is crucial for parasite survival. LPG has several detrimental effects on macrophage function, including inhibition of periphagosomal filamentous actin (F-actin) breakdown during phagosomal maturation. However, in RAW 264.7 macrophages pre-stimulated with lipopolysaccharide (LPS) and interferon ? (IFN?), known to up-regulate inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production, L. donovani promastigotes are unable to inhibit periphagosomal F-actin breakdown and phagosomal maturation proceeds normally. Moreover, the iNOS inhibitor aminoguanidine, blocked the positive effects of LPS/IFN? suggesting that NO is a key player in F-actin remodeling. In conclusion, production of NO by stimulated macrophages seems to allow phagosomal maturation following uptake of L. donovani promastigotes, suggesting a novel mechanism whereby NO facilitates killing of an intracellular pathogen. © 2007 Elsevier Inc. All rights reserved.

Keyword

Actin

AG

aminoguanidine

bovine serum albumine

BSA

cGMP

F-actin

filamentous actin

gamma Interferon

GFP

green fluorescent protein

guanosine 3':5'-cyclic monophosphate

IFN?

inducible nitric oxide synthase

iNOS

Leishmania donovani

lipophosphoglycan

lipopolysaccharide

LPG

LPS

Maturation

Nitric oxide

nitric oxide

NO

paraformaldehyde

PFA

Phagosome

MEDICINE

MEDICIN

Publication and Content Type

ref (subject category)

art (subject category)