(HOME) Subject: iron/chelate/bacteria
Immunology 1998 Aug;94(4):488-95
Interferon-gamma-activated primary enterocytes inhibit Toxoplasma gondii
replication: a role for intracellular iron.
Dimier IH, Bout DT
CJF INSERM 93-09 'Immunologie des Maladies Infectieuses', Equipe
associee INRA 'Immunologie Parasitaire', UFR des Sciences
Pharmaceutiques, Tours, France.
Toxoplasma gondii is an obligate intracellular parasite that infects a
wide variety of nucleated cells in its numerous intermediate hosts
including man. The oral route is the natural portal of entry of T.
gondii. Ingested organisms are released from cysts or oocysts within
the gastrointestinal tract and initially invade the intestinal
epithelium. We show that T. gondii invades and proliferates in
cultured primary rat enterocytes, obtained with an original procedure.
Activation of the enterocytes with rat recombinant interferon-gamma
(IFN-gamma) inhibits T. gondii replication, the inhibition being dose
dependent. Neither nitrogen and oxygen derivatives nor tryptophan
starvation appear to be involved in the inhibition of parasite
replication by IFN-gamma. Experiments using Fe2+ salt, carrier and
chelator indicate that intracellular T. gondii replication is iron
dependent, suggesting that IFN-gamma-treated enterocytes inhibit T.
gondii replication by limiting the availability of intracellular iron
to the parasite. Our data show that enterocytes probably play a major
role on mucosal surfaces as a first line of defence against this
coccidia, and possibly other pathogens, through an immune mechanism.
The results suggest that limiting the availability of iron could
represent a broad antimicrobial mechanism through which the activated
enterocytes exert control over intracellular pathogens.
PMID: 9767436, UI: 98440381
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Antimicrob Agents Chemother 1996 May;40(5):1298-1300
Trophozoite elimination in a rat model of Pneumocystis carinii pneumonia by
clinically achievable plasma deferoxamine concentrations.
Merali S, Chin K, Grady RW, Clarkson AB Jr
Department of Medical and Molecular Parasitology, New York University
School of Medicine, New York 10016, USA.
In a rat model of Pneumocystis carinii pneumonia, a 3-week infusion of
deferoxamine producing concentrations in plasma of > or = 1.5
micrograms m-1 eliminated the trophozoite life cycle stage. Since this
concentration is well below that routinely achieved in patients
treated for iron overload, deferoxamine has promise as a therapy for
AIDS-associated P.carinii pneumonia.
PMID: 8723489, UI: 96300560
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