Related Experiment Video
Updated: Jun 26, 2026
09:51
Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
Published on: July 26, 2017
Inductive and suppressive networks regulate TLR9-dependent gene expression in vivo
Sven Klaschik1, Debra Tross, Dennis M Klinman
1Laboratory of Experimental Immunology, Cancer and Inflammation Program, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
Journal of Leukocyte Biology
|January 31, 2009
Summary
CpG DNA stimulates innate immunity via Toll-like receptor 9 (TLR9). This study reveals TLR9-mediated gene expression occurs in waves, regulated by specific "major" and "minor" inducers, offering new insights into immune response control.
Area of Science:
- Immunology
- Bioinformatics
- Genomics
Background:
- Bacterial DNA with unmethylated CpG motifs activates Toll-like receptor 9 (TLR9), initiating innate immune responses.
- While CpG-mediated signaling is known, the full extent of TLR9-dependent gene expression remains unclear.
Purpose of the Study:
- To elucidate the complex regulatory networks governing TLR9-mediated gene expression.
- To characterize the temporal dynamics of gene induction following CpG stimulation.
Main Methods:
- Mice were treated with immunostimulatory CpG oligonucleotides (ODN).
- Splenic mRNA levels were analyzed using microarrays over 3 days.
- Bioinformatic analysis was applied to identify gene regulatory networks.
Main Results:
- CpG-induced immune stimulation occurs in multiple temporal waves.
- Gene upregulation is driven by temporally activated "major" and "minor" inducers.
- Bioinformatic analysis accurately identified in vivo CpG ODN-driven gene interactions, confirmed in TNF knockout mice.
Conclusions:
- This study reveals novel, global insights into TLR9-mediated gene activation networks.
- Identified regulatory networks provide a deeper understanding of TLR-mediated host defense.
- Findings facilitate the development of optimized immune response interventions.
Related Concept Videos
02:26NF-κB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
01:58Prokaryotic Transcriptional Activators and Repressors
The organization of prokaryotic genes in their genome is notably different from that of eukaryotes. Prokaryotic genes are organized, such that the genes for proteins involved in the same biochemical process or function are located together in groups. This group of genes, along with their regulatory elements, are collectively known as an operon. The functional genes in an operon are transcribed together to give a single strand of mRNA known as polycistronic mRNA.
Transcription of prokaryotic...
Transcription of prokaryotic...
01:58Prokaryotic Transcriptional Activators and Repressors
The organization of prokaryotic genes in their genome is notably different from that of eukaryotes. Prokaryotic genes are organized, such that the genes for proteins involved in the same biochemical process or function are located together in groups. This group of genes, along with their regulatory elements, are collectively known as an operon. The functional genes in an operon are transcribed together to give a single strand of mRNA known as polycistronic mRNA.
Transcription of prokaryotic...
Transcription of prokaryotic...
01:28Gene Regulation in Microbial Communities: Quorum Sensing
Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...
01:21Repressible Operon: trp Operon
The trp operon in Escherichia coli exemplifies a repressible operon. It regulates the synthesis of tryptophan through repressor-mediated transcriptional control and attenuation. This dual regulatory mechanism ensures tryptophan biosynthesis occurs only when needed, conserving cellular resources.Structure of the trp OperonThe trp operon consists of five structural genes (trpE, trpD, trpC, trpB, and trpA) that encode enzymes for tryptophan biosynthesis. These genes are transcribed as a single...
01:27Constitutive and Regulated Gene Expression
Gene expression in prokaryotes is governed by constitutive and regulated systems, allowing cells to balance the production of essential proteins with adaptive responses to environmental changes.Constitutive Gene ExpressionConstitutive, or housekeeping, genes are continuously expressed as they encode proteins vital for fundamental cellular processes. These include enzymes for glycolysis, ribosomal components for protein synthesis, and proteins involved in DNA replication. Their constant...