Limits...
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.

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

Analysis of cytokines in bdh2- mice. (A) Quantification of mRNAs for indicated cytokines in liver samples of control or bdh2- mice 36 h after infection with E. coli H9049. Expression levels of cytokine mRNAs as indicated with control mice set at 1. The relative mRNA levels in each sample were normalized to actin mRNA. Results show pooled data from two independent experiments, each with at least three mice per group. Statistical analysis by two-tailed unpaired Student’s t test: ns, not significant; *, P < 0.05. (B) Quantitative analysis of mRNAs for indicated cytokines in liver samples of control or bdh2- mice 6 h after LPS injection. Values relative to the liver mRNA from PBS-injected mice. Results show pooled data from two independent experiments, each with at least three mice per group. Statistical analysis by one-way analysis of variance followed by the Tukey HSD test for multiple comparisons: ns, not significant; *, P < 0.05; **, P < 0.01.
© Copyright Policy - openaccess
Related In: Results  -  Collection

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

fig5: Analysis of cytokines in bdh2- mice. (A) Quantification of mRNAs for indicated cytokines in liver samples of control or bdh2- mice 36 h after infection with E. coli H9049. Expression levels of cytokine mRNAs as indicated with control mice set at 1. The relative mRNA levels in each sample were normalized to actin mRNA. Results show pooled data from two independent experiments, each with at least three mice per group. Statistical analysis by two-tailed unpaired Student’s t test: ns, not significant; *, P < 0.05. (B) Quantitative analysis of mRNAs for indicated cytokines in liver samples of control or bdh2- mice 6 h after LPS injection. Values relative to the liver mRNA from PBS-injected mice. Results show pooled data from two independent experiments, each with at least three mice per group. Statistical analysis by one-way analysis of variance followed by the Tukey HSD test for multiple comparisons: ns, not significant; *, P < 0.05; **, P < 0.01.

Mentions: Cellular iron levels are altered in siderophore-deficient cells (Devireddy et al., 2010) and alterations in cellular iron levels have been shown to modulate cytokine production (Wessling-Resnick, 2010). Therefore we evaluated cytokine levels in WT or bdh2- mice challenged with LPS or E. coli strain H9049 to determine the effect of siderophore deficiency. As expected, IL-1β, IL-12b, IL-10, IFN-γ, and TNF were increased in a quantitative real-time PCR assay after LPS or E. coli challenge in WT mice (Fig. 5). Surprisingly, bdh2 deficiency only affected the expression of IFN-γ, under similar conditions (Fig. 5 A). Further, IFN-γ levels were also induced by challenge with PAM3-CSK4, a TLR2 agonist (not depicted). Observation of enhanced IFN-γ in bdh2- mice upon stimulation with TLR ligands is significant because IFN-γ limits the availability of iron in macrophages (Nairz et al., 2008). Thus, differential regulation of IFN-γ in bdh2- mice may aid the host by modulating iron availability in phagocytes limiting bacterial proliferation.


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 cytokines in bdh2- mice. (A) Quantification of mRNAs for indicated cytokines in liver samples of control or bdh2- mice 36 h after infection with E. coli H9049. Expression levels of cytokine mRNAs as indicated with control mice set at 1. The relative mRNA levels in each sample were normalized to actin mRNA. Results show pooled data from two independent experiments, each with at least three mice per group. Statistical analysis by two-tailed unpaired Student’s t test: ns, not significant; *, P < 0.05. (B) Quantitative analysis of mRNAs for indicated cytokines in liver samples of control or bdh2- mice 6 h after LPS injection. Values relative to the liver mRNA from PBS-injected mice. Results show pooled data from two independent experiments, each with at least three mice per group. Statistical analysis by one-way analysis of variance followed by the Tukey HSD test for multiple comparisons: ns, not significant; *, P < 0.05; **, P < 0.01.
© Copyright Policy - openaccess
Related In: Results  -  Collection

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

fig5: Analysis of cytokines in bdh2- mice. (A) Quantification of mRNAs for indicated cytokines in liver samples of control or bdh2- mice 36 h after infection with E. coli H9049. Expression levels of cytokine mRNAs as indicated with control mice set at 1. The relative mRNA levels in each sample were normalized to actin mRNA. Results show pooled data from two independent experiments, each with at least three mice per group. Statistical analysis by two-tailed unpaired Student’s t test: ns, not significant; *, P < 0.05. (B) Quantitative analysis of mRNAs for indicated cytokines in liver samples of control or bdh2- mice 6 h after LPS injection. Values relative to the liver mRNA from PBS-injected mice. Results show pooled data from two independent experiments, each with at least three mice per group. Statistical analysis by one-way analysis of variance followed by the Tukey HSD test for multiple comparisons: ns, not significant; *, P < 0.05; **, P < 0.01.
Mentions: Cellular iron levels are altered in siderophore-deficient cells (Devireddy et al., 2010) and alterations in cellular iron levels have been shown to modulate cytokine production (Wessling-Resnick, 2010). Therefore we evaluated cytokine levels in WT or bdh2- mice challenged with LPS or E. coli strain H9049 to determine the effect of siderophore deficiency. As expected, IL-1β, IL-12b, IL-10, IFN-γ, and TNF were increased in a quantitative real-time PCR assay after LPS or E. coli challenge in WT mice (Fig. 5). Surprisingly, bdh2 deficiency only affected the expression of IFN-γ, under similar conditions (Fig. 5 A). Further, IFN-γ levels were also induced by challenge with PAM3-CSK4, a TLR2 agonist (not depicted). Observation of enhanced IFN-γ in bdh2- mice upon stimulation with TLR ligands is significant because IFN-γ limits the availability of iron in macrophages (Nairz et al., 2008). Thus, differential regulation of IFN-γ in bdh2- mice may aid the host by modulating iron availability in phagocytes limiting bacterial proliferation.

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