Leishmania chagasi: Effect of the iron deficiency on the infection in BALB/c mice

Malafaia, Guilherme; Marcon, Leticia; Pereira, Liliane de Fátima; Pedrosa, Maria Lúcia; Rezende, Simone Aparecida

doi:10.1016/j.exppara.2010.11.010

Cited by 20 publications

(15 citation statements)

References 15 publications

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“…Observations regarding the effects of iron chelators on Leishmania growth are conflicting. Treatment of mice with desferrioxamine (DFO) led to the decrease of L. infantum proliferation [57] but not that of L. major [12]. Also, in in vitro models of macrophage infection, DFO has shown either no effect [58] or an inhibitory effect [59], [60], [61] on Leishmania growth.…”

Section: Discussionmentioning

confidence: 99%

Iron Overload Favors the Elimination of Leishmania infantum from Mouse Tissues through Interaction with Reactive Oxygen and Nitrogen Species

et al. 2013

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Iron plays a central role in host-parasite interactions, since both intervenients need iron for survival and growth, but are sensitive to iron-mediated toxicity. The host's iron overload is often associated with susceptibility to infection. However, it has been previously reported that iron overload prevented the growth of Leishmania major, an agent of cutaneous leishmaniasis, in BALB/c mice. In order to further clarify the impact of iron modulation on the growth of Leishmania in vivo, we studied the effects of iron supplementation or deprivation on the growth of L. infantum, the causative agent of Mediterranean visceral leishmaniasis, in the mouse model. We found that dietary iron deficiency did not affect the protozoan growth, whereas iron overload decreased its replication in the liver and spleen of a susceptible mouse strain. The fact that the iron-induced inhibitory effect could not be seen in mice deficient in NADPH dependent oxidase or nitric oxide synthase 2 suggests that iron eliminates L. infantum in vivo through the interaction with reactive oxygen and nitrogen species. Iron overload did not significantly alter the mouse adaptive immune response against L. infantum. Furthermore, the inhibitory action of iron towards L. infantum was also observed, in a dose dependent manner, in axenic cultures of promastigotes and amastigotes. Importantly, high iron concentrations were needed to achieve such effects. In conclusion, externally added iron synergizes with the host's oxidative mechanisms of defense in eliminating L. infantum from mouse tissues. Additionally, the direct toxicity of iron against Leishmania suggests a potential use of this metal as a therapeutic tool or the further exploration of iron anti-parasitic mechanisms for the design of new drugs.

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Section: Discussionmentioning

confidence: 99%

Iron Overload Favors the Elimination of Leishmania infantum from Mouse Tissues through Interaction with Reactive Oxygen and Nitrogen Species

et al. 2013

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“…Manipulation of host iron status through the use of chelators or supplemental iron has produce conflicting outcomes. For example, treatment of mice with desferroxamine for 2 weeks resulted in reduced L. chagasi burden in both the liver and spleen [116]. In contrast, parenteral iron supplementation protected mice against Leishmania major, however this outcome appears to be the result of an enhanced immune response as the oxidative burst was enhanced in the iron treated animals [117].…”

Section: Global Diseases Influenced By Iron Statusmentioning

confidence: 99%

Iron metabolism and the innate immune response to infection

Johnson

Wessling‐Resnick

2012

Microbes and Infection

219

160

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Host antimicrobial mechanisms reduce iron availability to pathogens. Iron proteins influencing the innate immune response include hepcidin, lactoferrin, siderocalin, haptoglobin, hemopexin, Nramp1, ferroportin and the transferrin receptor. Numerous global health threats are influenced by iron status and provide examples of our growing understanding of the connections between infection and iron metabolism.

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“…However, DFO has shown either no effect (Murray et al, 1991) or an inhibitory effect on the intramacrophagic growth of L. donovani (Segovia et al, 1989; Das et al, 2009) and L. amazonensis (Borges et al, 1998). Moreover, treatment of mice with DFO does not affect the development of skin lesions caused by L. major (Bisti et al, 2000), but reduces the hepatic and splenic growth of L. infantum (Malafaia et al, 2011). Conversely, feeding mice with an iron-deficient diet did not influence L. infantum proliferation (Vale-Costa et al, 2013).…”

Section: Iron Metabolism In Leishmania Infectionmentioning

confidence: 99%

Iron in intracellular infection: to provide or to deprive?

Silva‐Gomes

Vale-Costa

Appelberg

et al. 2013

Front. Cell. Infect. Microbiol.

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Due to their chemical versatility, transition metals were incorporated as cofactors for several basic metabolic pathways in living organisms. This same characteristic makes them potentially harmful, since they can be engaged in deleterious reactions like Fenton chemistry. As such, organisms have evolved highly specialized mechanisms to supply their own metal needs while keeping their toxic potential in check. This dual character comes into play in host-pathogen interactions, given that the host can either deprive the pathogen of these key nutrients or exploit them to induce toxicity toward the invading agent. Iron stands as the prototypic example of how a metal can be used to limit the growth of pathogens by nutrient deprivation, a mechanism widely studied in Mycobacterium infections. However, the host can also take advantage of iron-induced toxicity to control pathogen proliferation, as observed in infections caused by Leishmania. Whether we may harness either of the two pathways for therapeutical purposes is still ill-defined. In this review, we discuss how modulation of the host iron availability impacts the course of infections, focusing on those caused by two relevant intracellular pathogens, Mycobacterium and Leishmania.

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Leishmania chagasi: Effect of the iron deficiency on the infection in BALB/c mice

Cited by 20 publications

References 15 publications

Iron Overload Favors the Elimination of Leishmania infantum from Mouse Tissues through Interaction with Reactive Oxygen and Nitrogen Species

Iron Overload Favors the Elimination of Leishmania infantum from Mouse Tissues through Interaction with Reactive Oxygen and Nitrogen Species

Iron metabolism and the innate immune response to infection

Iron in intracellular infection: to provide or to deprive?

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