The prevention of the growth of Leishmania major progeny in BALB/c iron-loaded mice: a process coupled to increased oxidative burst, the amplitude and duration of which depend on initial parasite developmental stage and dose.
BALB/c mice were given or not iron around the time of intradermal parasite inoculation, in their ears, of either 10(6) stationary-phase (designated "high-dose model") or 10(3)Leishmania major metacyclic promastigotes (designated "low-dose model"). Iron-loaded mice in the high-dose model displayed delayed and limited pathogenic processes, whereas in the low-dose model, the mice remained ear lesion-free over 12 months post-parasite inoculation. These phenotypes were coupled to an increased leukocyte oxidative burst displayed mainly by neutrophils: it was early and transient in the high-dose model, whereas it was sustained in the low-dose model. In the latter model, injection of an antioxidant (diphenyleneiodonium chloride) at week 2 post-L. major inoculation resulted in a significant decrease in oxidative burst and reversed the protective status. The increased and sustained oxidative burst displayed by the neutrophils, the sustained presence of IL-12 (p40/p70)-positive leukocytes in the ear dermis, the low number of inflammatory leukocytes in the ear dermis and their concomitant high number in the draining lymph node are three related features that likely contribute to the shaping of the protective status, the onset and dynamic maintenance of which are antioxidant sensitive.
Bisti
Sylvia
S
Laboratory of Molecular Parasitology, Hellenic Pasteur Institute, 127 Vas. Sofias Avenue, 115 21 Athens, Greece.
Konidou
Georgia
G
Boelaert
Johan
J
Lebastard
Mai
M
Soteriadou
Ketty
K
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D004423:Ear / Q000469:parasitology; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007505:Iron-Dextran Complex / Q000494:pharmacology*; D018320:Leishmania major / Q000254:growth & development*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology*; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D009861:Onium Compounds / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects* / Q000276:immunology; D013047:Specific Pathogen-Free Organisms
D000975:Antioxidants; D009861:Onium Compounds; D017382:Reactive Oxygen Species; C007517:diphenyleneiodonium; D007505:Iron-Dextran Complex