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Regulation of mammalian siderophore 2,5-DHBA in the innate immune response to infection.

Liu Z, Reba S, Chen WD, Porwal SK, Boom WH, Petersen RB, Rojas R, Viswanathan R, Devireddy L - J. Exp. Med. (2014)

Bottom Line: Pathogens secrete small iron-binding moieties, siderophores, to acquire host iron.In support of this idea, supplementation with mammalian siderophore enhances bacterial growth in vitro.Thus, reciprocal regulation of 24p3 and mammalian siderophore is a protective mechanism limiting microbial access to iron.

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Affiliation: Case Comprehensive Cancer Center; Department of Pathology; Department of Medicine, Tuberculosis Research Institute and Division of Infectious Diseases; and Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106Case Comprehensive Cancer Center; Department of Pathology; Department of Medicine, Tuberculosis Research Institute and Division of Infectious Diseases; and Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106.

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Analysis of iron parameters in E. coli H9049–infected WT and bdh2- mice. (A) Serum iron in naive and E. coli H9049–infected C57BL/6 WT and bdh2- mice. Mice were infected with 6 × 107 CFU of E. coli H9049 and serum iron was determined 3 and 6 h after infection. Data are representative of two independent experiments, each with at least three mice per group. Statistical analysis by two-tailed unpaired Student’s t test: *, P < 0.05. (B) Quantification of hepcidin mRNA in WT or bdh2- mice 3 or 6 h after infection with 6 × 107 CFU of E. coli H9049. Expression levels of hepcidin mRNA in control mice was set at 1. The relative mRNA levels in each mouse were normalized to actin mRNA. Data are representative of two independent experiments, each with at least three mice per group. Statistical analysis by two-tailed unpaired Student’s t test: *, P < 0.05; **, P < 0.01. (C) Immunoblot analysis of ferroportin in spleen samples from WT or bdh2- mice infected with 6 × 107 CFU of E. coli H9049. Actin was used as a loading control. Spleen samples from three mice were used. Molecular weight markers are indicated on the right.
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fig7: Analysis of iron parameters in E. coli H9049–infected WT and bdh2- mice. (A) Serum iron in naive and E. coli H9049–infected C57BL/6 WT and bdh2- mice. Mice were infected with 6 × 107 CFU of E. coli H9049 and serum iron was determined 3 and 6 h after infection. Data are representative of two independent experiments, each with at least three mice per group. Statistical analysis by two-tailed unpaired Student’s t test: *, P < 0.05. (B) Quantification of hepcidin mRNA in WT or bdh2- mice 3 or 6 h after infection with 6 × 107 CFU of E. coli H9049. Expression levels of hepcidin mRNA in control mice was set at 1. The relative mRNA levels in each mouse were normalized to actin mRNA. Data are representative of two independent experiments, each with at least three mice per group. Statistical analysis by two-tailed unpaired Student’s t test: *, P < 0.05; **, P < 0.01. (C) Immunoblot analysis of ferroportin in spleen samples from WT or bdh2- mice infected with 6 × 107 CFU of E. coli H9049. Actin was used as a loading control. Spleen samples from three mice were used. Molecular weight markers are indicated on the right.

Mentions: Serum iron levels are decreased during infection to starve the invading bacteria of iron (Ganz, 2009). Hypoferremia associated with infection is mediated by hepcidin (Ganz and Nemeth, 2012; Drakesmith and Prentice, 2012). Naive bdh2- mice have lower serum iron when compared with WT mice (Fig. 7 A). However, upon injection of sublethal doses of E. coli, serum iron was even lower in bdh2- mice compared with E. coli–injected WT mice (Fig. 7 A). The reduction in serum iron in the absence of 2,5-DHBA further restricts bacterial replication in bdh2- mice.


Regulation of mammalian siderophore 2,5-DHBA in the innate immune response to infection.

Liu Z, Reba S, Chen WD, Porwal SK, Boom WH, Petersen RB, Rojas R, Viswanathan R, Devireddy L - J. Exp. Med. (2014)

Analysis of iron parameters in E. coli H9049–infected WT and bdh2- mice. (A) Serum iron in naive and E. coli H9049–infected C57BL/6 WT and bdh2- mice. Mice were infected with 6 × 107 CFU of E. coli H9049 and serum iron was determined 3 and 6 h after infection. Data are representative of two independent experiments, each with at least three mice per group. Statistical analysis by two-tailed unpaired Student’s t test: *, P < 0.05. (B) Quantification of hepcidin mRNA in WT or bdh2- mice 3 or 6 h after infection with 6 × 107 CFU of E. coli H9049. Expression levels of hepcidin mRNA in control mice was set at 1. The relative mRNA levels in each mouse were normalized to actin mRNA. Data are representative of two independent experiments, each with at least three mice per group. Statistical analysis by two-tailed unpaired Student’s t test: *, P < 0.05; **, P < 0.01. (C) Immunoblot analysis of ferroportin in spleen samples from WT or bdh2- mice infected with 6 × 107 CFU of E. coli H9049. Actin was used as a loading control. Spleen samples from three mice were used. Molecular weight markers are indicated on the right.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4042634&req=5

fig7: Analysis of iron parameters in E. coli H9049–infected WT and bdh2- mice. (A) Serum iron in naive and E. coli H9049–infected C57BL/6 WT and bdh2- mice. Mice were infected with 6 × 107 CFU of E. coli H9049 and serum iron was determined 3 and 6 h after infection. Data are representative of two independent experiments, each with at least three mice per group. Statistical analysis by two-tailed unpaired Student’s t test: *, P < 0.05. (B) Quantification of hepcidin mRNA in WT or bdh2- mice 3 or 6 h after infection with 6 × 107 CFU of E. coli H9049. Expression levels of hepcidin mRNA in control mice was set at 1. The relative mRNA levels in each mouse were normalized to actin mRNA. Data are representative of two independent experiments, each with at least three mice per group. Statistical analysis by two-tailed unpaired Student’s t test: *, P < 0.05; **, P < 0.01. (C) Immunoblot analysis of ferroportin in spleen samples from WT or bdh2- mice infected with 6 × 107 CFU of E. coli H9049. Actin was used as a loading control. Spleen samples from three mice were used. Molecular weight markers are indicated on the right.
Mentions: Serum iron levels are decreased during infection to starve the invading bacteria of iron (Ganz, 2009). Hypoferremia associated with infection is mediated by hepcidin (Ganz and Nemeth, 2012; Drakesmith and Prentice, 2012). Naive bdh2- mice have lower serum iron when compared with WT mice (Fig. 7 A). However, upon injection of sublethal doses of E. coli, serum iron was even lower in bdh2- mice compared with E. coli–injected WT mice (Fig. 7 A). The reduction in serum iron in the absence of 2,5-DHBA further restricts bacterial replication in bdh2- mice.

Bottom Line: Pathogens secrete small iron-binding moieties, siderophores, to acquire host iron.In support of this idea, supplementation with mammalian siderophore enhances bacterial growth in vitro.Thus, reciprocal regulation of 24p3 and mammalian siderophore is a protective mechanism limiting microbial access to iron.

View Article: PubMed Central - HTML - PubMed

Affiliation: Case Comprehensive Cancer Center; Department of Pathology; Department of Medicine, Tuberculosis Research Institute and Division of Infectious Diseases; and Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106Case Comprehensive Cancer Center; Department of Pathology; Department of Medicine, Tuberculosis Research Institute and Division of Infectious Diseases; and Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106.

Show MeSH
Related in: MedlinePlus