Asthma, CpG DNA and Toll-like Receptor-9

What is the cause of asthma?

Reduced exposure in early life to microbes and microbial products is thought to cause asthma. People who were raised on farms and who attended out-of-home daycare earlier have fewer and less severe atopic disorders. The notion of “atopic disorder” describes a wide range of genetically mediated allergic diseases. The list includes allergic rhinitis, asthma, and atopic dermatitis (AD) associated with heightened T-helper type 2-driven inflammatory responses to common allergens, especially inhaled and food allergens.

The exact causes of asthma are not yet known. Many different reasons may contribute to asthma. Many environmental factors may trigger asthma in people sensitive to this atopic disorder.


(Source: https://simple.wikipedia.org/wiki/Asthma).

Bacterial DNA, which differs from mammalian DNA in the frequency of cytosine-guanine (CpG) dinucleotides, is an immune-stimulating substance. CpG oligonucleotides (CpG ODNs) induce type 1 T helper (Th1) cells to produce Th1 cytokines (interferon-γ, interleukin-2, and tumor necrosis factor-β) to activate macrophages. Macrophages are responsible for cell-mediated immunity and phagocyte-dependent protective responses.

Scientists have speculated that CpG ODNs may help prevent or reverse the white blood cell-linked (eosinophilic) inflammation of atopic asthma. Inducing the regulatory-type responses of T cells and antigen-presenting cells with CpG ODNs is thought to protect against atopic diseases such as asthma. Ongoing clinical trials examine CpG ODNs used alone and as adjuvants for immunotherapy in human populations with atopic diseases.

Bacterial and viral DNA oligodeoxynucleotides containing unmethylated cytosine-guanine (CpG) dinucleotides are found much more frequently than in vertebrates. These strongly immune-active CpG ODNs induce the proliferation and activation of B cells. 

In recent decades, research scientists identified additional specific immune responses to CpG dinucleotide DNA in molecular pathways linking recognition of the CpG ligand with its effects. A limited number of human immune cells, most notably plasmacytoid DCs and B cells, constitutively express the receptor for CpG DNA, TLR-9.

CpG DNA enters cells through a process called endocytosis, in which cells absorb external substances by engulfing them with the cell membrane. After entering the cell, TLR-9 recognizes CpG oligonucleotides and translocate them to the nucleus, where they activate the nuclear factor-κB.

The early effects of exposure primarily lead to increased innate immune responses. Activated B cells and plasmacytoid DCs release IL-10, type-I IFNs, IL-12, IFN-inducible protein-10, and other cytokines and chemokines, inducing a regulatory/Th1-oriented inflammatory milieu. 

Natural killer cells, T cells, and others that amplify and modulate the immune response react to these molecules. The induction of costimulatory receptors, immunoglobulin isotype switching by B-cells, and the activation of a cascade of cellular responses promoting adaptive immune responses are later effects.


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