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Updated: Aug 25, 2026
Neisseria meningitidis Infection of Induced Pluripotent Stem-Cell Derived Brain Endothelial Cells
Published on: July 14, 2020
Expression of epithelial cell iron-related genes upon infection by Neisseria meningitidis
Robert A Bonnah1, Martina U Muckenthaler, Hanqian Carlson
1Vaccine and Gene Therapy Institute, Oregon Health and Sciences University, Portland, OR, USA.
Abstract:
Infection by the obligate human pathogens Neisseria meningitidis (MC) and Neisseria gonorrhoeae (GC) reduces the expression of host epithelial cell transferrin receptor 1 (TfR-1) (Bonnah et al., 2000, Cellular Microbiology 2: 207-218). In addition, the rate and pattern of TfR-1 cycling is altered, leading to diminished uptake of Tf-iron by infected host cells. As Tf-iron is important for maintaining iron homeostasis in the eukaryotic cell, these findings raised the possibility that Neisseria infection might affect further pathways of epithelial cell iron metabolism. We used a specialized cDNA microarray platform, the 'IronChip', to investigate the expression of genes involved in iron transport, storage and regulation. We show that mRNA expression of several host genes involved in iron homeostasis is altered. Surprisingly, the general mRNA expression profile of infected cells closely resembled that of uninfected cells grown in an iron-limited environment. An important exception to this profile is TfR-1, the mRNA level of which is strongly reduced. Low TfR-1 expression may be explained in part by decreased activity of the iron-regulatory proteins (IRPs) in MC-infected cells, which may result in the destabilization of TfR-1 mRNA. Intriguingly, low IRP activity contrasts with the decrease in H-ferritin protein levels in infected cells. This finding suggests that low IRP activity may be responsible in part for the decrease in TfR-1 mRNA levels. A discussion of these novel findings in relation to MC infection and virulence is provided.
Insights
Neisseria infections alter host cell iron metabolism by reducing transferrin receptor 1 (TfR-1) expression. This mimics an iron-limited environment, impacting iron homeostasis and potentially influencing Neisseria virulence.
Area of Science:
- Microbiology
- Molecular Biology
- Cell Biology
Background:
- Neisseria meningitidis (MC) and Neisseria gonorrhoeae (GC) infections reduce host epithelial cell transferrin receptor 1 (TfR-1) expression.
- Altered TfR-1 cycling diminishes transferrin-iron uptake in infected cells, impacting cellular iron homeostasis.
Purpose of the Study:
- To investigate the impact of Neisseria infection on host epithelial cell iron metabolism pathways.
- To analyze the expression of genes involved in iron transport, storage, and regulation using a specialized cDNA microarray.
Main Methods:
- Utilized a specialized cDNA microarray platform, the 'IronChip', to assess gene expression.
- Compared gene expression profiles of infected and uninfected host cells, particularly focusing on iron homeostasis-related genes.
Main Results:
- Neisseria infection altered the mRNA expression of several host genes involved in iron homeostasis.
- Infected cells exhibited a gene expression profile similar to uninfected cells in an iron-limited environment, with significantly reduced TfR-1 mRNA levels.
- Decreased iron-regulatory protein (IRP) activity in MC-infected cells may contribute to TfR-1 mRNA destabilization, contrasting with reduced H-ferritin protein levels.
Conclusions:
- Neisseria infection profoundly affects host epithelial cell iron metabolism, mimicking iron-limited conditions.
- Reduced TfR-1 expression, potentially mediated by decreased IRP activity, is a key feature of MC infection.
- These alterations in host iron metabolism may play a role in Neisseria pathogenesis and virulence.
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