Role Of Iron In Infection Research Articles

Role of iron in infection

Role of iron in infection

The Re-Emerging Role of Iron in Infection and Immunity

The Re-Emerging Role of Iron in Infection and Immunity

Pathobiology of the role of iron in infection.

Beyond its role in hemoglobin synthesis, iron plays an important part in host defense mechanisms. Sequestration of iron is a mechanism to control bacterial proliferation and virulence. However, uremia results in several immunologic deficits, including impaired lymphocyte mitogenic response and granulocyte function abnormalities such as impaired phagocytosis, respiratory burst, and myeloperoxidase activity. At the other end of the spectrum, iron overload can impair immune function and stimulate bacterial growth and virulence. Overtreatment with iron increases the preexisting risk of infectious complications for uremic patients, as indicated by hyperferritinemia in hemodialysis patients who have impaired polymorphonuclear leukocyte (PMNL)-induced bacterial killing. These results suggest that maintaining iron status within normal range is important to control potential increased risk of infection in patients with end-stage renal disease (ESRD).

Intravenous iron therapy: well‐tolerated, yet not harmless

In the majority of patients with chronic renal failure, it is essential to substitute erythropoietic agents and iron to maintain a haemoglobin level above 11 g dL-1. Intravenous iron is more effective than oral iron. Substitution of intravenous iron is mainly performed using iron(III)-hydroxide-sucrose complex (iron sucrose) and iron(III)-sodium-gluconate in sucrose (iron gluconate), and is, in general, well-tolerated. Nonetheless, intravenous iron therapy has effects on endothelial cells, polymorphonuclear leucocytes and cytokines which are most likely related to non-transferrin bound labile iron. These effects suggest a role of iron in infection or atherosclerosis. Yet, not all available data support the association of iron with infection and atherosclerosis. A recent trial showed that iron sucrose is safe when given as treatment for iron deficiency or for maintenance of iron stores. Nevertheless, iron therapy should be handled with caution but its use should not be feared whenever indicated.

Impairment of transendothelial leukocyte migration by iron complexes.

Although iron sucrose and iron gluconate are generally well tolerated in patients who are treated for renal anemia, recent clinical studies and cell culture experiments suggested significant toxicity and long-term side effects arising from the use of these iron complexes. Because of the possible role of iron in infection or cardiovascular disease, it was theorized that parenteral iron compounds influence endothelial and PMN interaction in vitro. A well-established double-chamber method was used to assess the effect of different concentrations of iron sucrose and iron gluconate (1, 25, 50, and 100 micro g/ml) on the transendothelial migration of PMN. Preincubation of PMN and endothelial cells as well as preincubation of PMN alone with 25, 50, or 100 micro g/ml iron resulted in a significant decrease in PMN migration. In contrast, after incubation of the endothelial cells alone with iron, no reduction in the transendothelial migration of PMN was observed. Preincubation of PMN and/or endothelial cells with 1 micro g/ml iron did not lead to any decrease in the rate of migrated PMN. The only significant change in experiments with 1 micro g/ml was an increase in PMN migration after preincubation of endothelial cells and PMN with iron gluconate. A four-way ANOVA showed a significant effect of the iron concentration (P < 0.000001), of type of iron complex (P < 0.005), of the preincubation of endothelial cell (P < 0.001), and of the preincubation of PMN with iron (P < 0.000001) on PMN diapedesis. It is concluded that iron sucrose and iron gluconate cause a significant inhibition of transendothelial migration of PMN.

The role of iron in infections with intracellular bacteria

The requirement for iron as a critical component for cellular processes has long been appreciated. During infection with intracellular bacteria, iron is required by both the host cell and the pathogen that inhabits the host cell. Macrophages require iron as a cofactor for the execution of important antimicrobial effector mechanisms, including the NADPH dependent oxidative burst and the production of nitrogen radicals catalysed by the inducible nitric oxide synthase. On the other side of the equation, intracellular bacteria such as Salmonella typhimurium and Mycobacterium tuberculosis have an obligate requirement for iron to support their growth and survival inside cells. This brief report summarises the background to our work on iron modulation in infections with these two organisms and highlights key observations on how modulation of host iron status disturbs the equilibrium between host and pathogen and can determine the outcome of infection.

Hemochromatosis as a Risk Factor for Fulminant Staphylococcus aureus Pneumonia*

Hemochromatosis as a Risk Factor for Fulminant Staphylococcus aureus Pneumonia*

Pathobiology of the role of iron in infection

Beyond its role in hemoglobin synthesis, iron plays an important part in host defense mechanisms. Sequestration of iron is a mechanism to control bacterial proliferation and virulence. However, uremia results in several immunologic deficits, including impaired lymphocyte mitogenic response and granulocyte function abnormalities such as impaired phagocytosis, respiratory burst, and myeloperoxidase activity. At the other end of the spectrum, iron overload can impair immune function and stimulate bacterial growth and virulence. Overtreatment with iron increases the preexisting risk of infectious complications for uremic patients, as indicated by hyperferritinemia in hemodialysis patients who have impaired polymorphonuclear leukocyte (PMNL)-induced bacterial killing. These results suggest that maintaining iron status within normal range is important to control potential increased risk of infection in patients with end-stage renal disease (ESRD). Am J Kidney Dis 34:s25-s29, 1999. Copyright © 1999 by National Kidney Foundation

The role of iron in infection

The availability of iron plays a critical role in host-parasite relations. Microbial pathogens cannot replicate without acquiring iron from their vertebrate hosts, and several strategies of microbial iron acquisition have evolved. Vertebrate animals have developed elaborate strategies to withhold iron from invading pathogens while retaining their own access to the metal. This review focuses on recent data from studies of both microbial iron-acquisition mechanisms and the vertebrate host's iron-withholding defense system components.

Elimination of the vitamin B12 uptake or synthesis pathway does not diminish the virulence of Escherichia coli K1 or Salmonella typhimurium in three model systems.

The role of iron in infection is of great importance and is well understood. During infection, both the host and the pathogen go through many complicated changes to regulate iron levels. Iron and vitamin B12 share certain features. For example, Escherichia coli has similar transport systems for both nutrients, and binding proteins for both are located in gastric juice, liver, saliva, granulocytes, and milk. It is because of such parallels between iron and B12 that we have explored the role of B12 in virulence. A btuB::Tn10 insertion which disrupts the gene encoding the vitamin B12 receptor from E. coli K-12 was P1 transduced into a virulent E. coli K1 strain. In both an infant-rat model and a chicken embryo model, no difference in virulence between the wild-type and the mutant strains was found. Strains of Salmonella typhimurium with mutations in the cobalamin synthesis pathway (Cob) and in btuB were used in a mouse model of virulence. Mutation of the Cob locus or of btuB does not decrease virulence. Interestingly, the inability to synthesize vitamin B12 actually increases virulence compared with the wild type in the S. typhimurium model. This effect is independent of the B12 intake of the mice.

Biological and Ultrastructural Aspects of Iron Overload: An Overview

The morphologic aspects of iron overload have been studied in human subjects, mammals, and birds with spontaneous overload, in a variety of experimental animals, and also in cell cultures. Reviewed here are the contributions of electron microscopy to the understanding of the iron-loading process, as reported during the last 12 years. The electron-density of ferrihydrite cores located within the protein shell of the ferritin molecule enabled its identification within either cytosol or lysosomes (siderosomes) of iron-exposed cells. The process of (holo)ferritin assembly, its transfer into siderosomes, and its degradation to hemosiderin can be followed in various cells. Siderosomes display cell-line-specific ultrastructural features, and different cell types show varying iron-segregating capacity. The study of experimental animals and cultured cells show that an iron-rich milieu may be damaging, probably through iron-catalyzed lipid peroxidation. Recent ultrastructural studies stress the value of describing initial alterations as opposed to the irrelevant end-stage findings. Further efforts should be directed toward elucidating the origin of iron in neonatal hemochromatosis, the role of iron in infection and neoplasia, and the nature and role of brain iron.

The Role of Crevicular Fluid Iron in Periodontal Disease.

This article presents a brief review of literature on the role of iron in infection and reports the concentration of iron in crevicular fluid (CF) in humans and beagle dogs. Crevicular fluid from human subjects was collected from gingivitis and periodontitis sites. The CF from beagle dogs was collected from gingivitis and active periodontitis (ligature-induced) sites. The results showed that the concentration of iron in human CF was often higher than in human serum. Also, a comparison between CF collected from gingivitis sites and periodontitis sites revealed a significantly higher concentration of iron in CF collected from the periodontitis sites. The studies in ligature-induced periodontitis in beagle dogs revealed at least a 3-fold increase in iron concentration in CF following ligation compared to the preligation values. Based on the available literature it is suggested that high concentration of iron in CF is not due to serum transferrin or polymorphonuclear leukocyte lactoferrin. Also, this high concentration of iron in CF might play an important role in enhancement of growth and virulence of microorganisms of the subgingival plaque and the initiation of active periodontitis.