Host-Pathogen Interactions: The Role of Iron1,

Doherty, Conor

doi:10.1093/jn/137.5.1341

Cited by 153 publications

(126 citation statements)

References 38 publications

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“…The proposed physiological rationale for these changes is nutrient deprivation to limit proliferation of the invading microbe (47). A well documented example is the contest between host and pathogen over limiting iron stores, which plays a critical role in determining the outcome of infection (48). In contrast, however, systemic copper concentrations are widely reported to increase in response to acute and chronic inflammation (49 -65).…”

Section: Discussionmentioning

confidence: 99%

A Role for the ATP7A Copper-transporting ATPase in Macrophage Bactericidal Activity

White

Lee

Kambe

et al. 2009

Journal of Biological Chemistry

440

547

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Copper is an essential micronutrient that is necessary for healthy immune function. This requirement is underscored by an increased susceptibility to bacterial infection in copper-deficient animals; however, a molecular understanding of its importance in immune defense is unknown. In this study, we investigated the effect of proinflammatory agents on copper homeostasis in RAW264.7 macrophages. Interferon-␥ was found to increase expression of the high affinity copper importer, CTR1, and stimulate copper uptake. This was accompanied by copper-stimulated trafficking of the ATP7A copper exporter from the Golgi to vesicles that partially overlapped with phagosomal compartments. Silencing of ATP7A expression attenuated bacterial killing, suggesting a role for ATP7A-dependent copper transport in the bactericidal activity of macrophages. Significantly, a copper-sensitive mutant of Escherichia coli lacking the CopA copper-transporting ATPase was hypersensitive to killing by RAW264.7 macrophages, and this phenotype was dependent on ATP7A expression. Collectively, these data suggest that copper-transporting ATPases, CopA and ATP7A, in both bacteria and macrophage are unique determinants of bacteria survival and identify an unexpected role for copper at the hostpathogen interface.

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Section: Discussionmentioning

confidence: 99%

A Role for the ATP7A Copper-transporting ATPase in Macrophage Bactericidal Activity

White

Lee

Kambe

et al. 2009

Journal of Biological Chemistry

440

547

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“…Ferritins, which can sequester iron, play dual roles in detoxification and iron storage (Arosio et al, 2009;Arosio and Levi, 2010), and the selenium-binding protein covalently binds selenium (Bansal et al, 1989;Jeong et al, 2009). Interestingly, iron appears to be essential for bacterial growth (Doherty, 2007), especially for Vibrio species (Wright et al, 1981;Tolmasky and Crosa, 1991;Wyckoff et al, 2007), and selenium is a trace element crucial for the survival of all living organisms through the formation of selenocysteine, a modified amino acid largely implicated in antioxidant defense (e.g. glutathione peroxidase, thioredoxin reductase) (Burk et al, 2003;Stadtman, 1996).…”

Section: Discussionmentioning

confidence: 99%

Physiological responses of the scleractinian coral Pocillopora damicornis to bacterial stress from Vibrio coralliilyticus

Vidal-Dupiol

Ladrière

Meistertzheim

et al. 2011

Journal of Experimental Biology

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SUMMARYAs the effects of climate change have become increasingly visible over the past three decades, coral reefs have suffered from a number of natural and anthropogenic disturbances that have caused a critical decline in coral populations. Among these disturbances are coral diseases, which have appeared with increasing frequency and severity, often in correlation with increases in water temperature. Although the crucial role played by Vibrio species in coral disease has been widely documented, the scientific community does not yet fully understand the infection process of Vibrio or its impact on coral physiology and immunology. Here, we investigated the physiological and transcriptomic responses of a major reef-building coral, Pocillopora damicornis, when exposed to a specific pathogen (Vibrio coralliilyticus) under virulent (increasing water temperature) and nonvirulent (constant low temperature) conditions. The infection process was examined by electron microscopy and quantitative reverse-transcription PCR, and coral health was monitored by visual observations and measurements of zooxanthellar density. The results obtained suggest that coral tissue invasion occurs upon increasing water temperature only. Transcriptomic variations were investigated using a suppression-subtractive-hybridization approach, and the expression levels of six candidate immunerelated genes were examined during bacterial exposure. These genes correspond to three lectin-like molecules putatively involved in the recognition of pathogens, two metal-binding proteins putatively involved in antibacterial response and one cystein protease inhibitor. The transcription patterns of these selected genes provide new insights into the responses of coral colonies to virulent versus non-virulent bacteria. Supplementary material available online at

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“…The interaction of iron and infection has been reviewed (Doherty, 2007). The relevance of a food-based intervention and a compartmentalized effect on iron metabolism can be seen in the light of the effects of iron supplementation in children in a malaria-endemic setting (Sazawal et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Influence of carotene-rich vegetable meals on the prevalence of anaemia and iron deficiency in Filipino schoolchildren

et al. 2010

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Objective: To determine the effects of eating carotene-rich green and yellow vegetables on the prevalence of anaemia, iron deficiency and iron-deficiency anaemia in schoolchildren. Subjects and methods: Schoolchildren (n ¼ 104), aged 9-12 years, received standardized meals containing 4.2 mg of provitamin A carotenoids/day (mainly b-carotene) from yellow and green leafy vegetables and at least 7 g dietary fat/day. The meals were provided three times/day, 5 days/week, for 9 weeks at school. Before and after the dietary intervention, total-body vitamin A pool size was assessed by using the deuterated-retinol-dilution method; serum retinol and b-carotene concentrations were measured by high-performance liquid chromatography; and whole blood haemoglobin (Hb) and zinc protoporphyrin (ZnPP) concentrations were measured by using a photometer and a hematofluorometer, respectively. Results: After 9 weeks, the mean total-body vitamin A pool size increased twofold (95% confidence interval (CI): À0.11, À0.07 mmol retinol; Po0.001), and serum b-carotene concentration increased fivefold (95% CI: À0.97, À0.79 mmol/l; Po0.001). Blood Hb (95% CI: À1.02, À0.52 g per 100 ml; Po0.001) and ZnPP increased (95% CI: À11.82, À4.57 mmol/mol haem; Po0.001). The prevalence of anaemia (Hbo11.5 g per 100 ml) decreased from 12.5 to 1.9% (Po0.001). There were no significant changes in the prevalence of iron deficiency or iron-deficiency anaemia. Conclusions: Ingestion of carotene-rich yellow and green leafy vegetables improves the total-body vitamin A pool size and Hb concentration, and decreases anaemia rates in Filipino schoolchildren, with no effect on iron deficiency or iron-deficiency anaemia rates.

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Host-Pathogen Interactions: The Role of Iron1,

Cited by 153 publications

References 38 publications

A Role for the ATP7A Copper-transporting ATPase in Macrophage Bactericidal Activity

A Role for the ATP7A Copper-transporting ATPase in Macrophage Bactericidal Activity

Physiological responses of the scleractinian coral Pocillopora damicornis to bacterial stress from Vibrio coralliilyticus

Influence of carotene-rich vegetable meals on the prevalence of anaemia and iron deficiency in Filipino schoolchildren

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