Oral administration of a synthetic agonist of Toll-like receptor 9 potently modulates peanut-induced allergy in mice.

Abstract

BACKGROUND:

Agonists of Toll-like receptor 9 have been shown to induce potent T(H)1-type immune responses and prevent and reverse ovalbumin-induced T(H)2-dominant allergic asthma in mice.

OBJECTIVE:

We examined oral administration of a synthetic agonist of Toll-like receptor 9 (immune modulatory oligonucleotide [IMO]) to modulate peanut-induced allergy in mice.

METHODS:

In the prevention model mice were sensitized 3 times by means of oral administration of peanut in the presence or absence of IMO. In a treatment protocol mice were sensitized orally with peanut on days 0 and 14 and treated 4 times with oral administration of IMO starting on day 21.

RESULTS:

In the prevention study mice that received the combination of IMO/peanut showed decreased IgE and increased IgG2a levels in the serum and intestinal tissue compared with mice sensitized with peanut only. In spleen cell recall experiments, production of IL-5 and IL-13 was inhibited and production of IFN-gamma was increased in mice immunized with the peanut/IMO combination compared with those sensitized with peanut only. In the treatment model IMO-treated mice showed decreased IgE, IL-5, and IL-13 levels and increased IgG2a and IFN-gamma levels in the serum, intestines, and spleen cells compared with PBS-treated mice. A reduction in local inflammation and restoration of normal structure in the intestines was found in the mice that received IMO in both models.

CONCLUSION:

These results indicate that IMOs can switch peanut-induced T(H)2 immune responses toward T(H)1 responses accompanied by reduced inflammation in the gastrointestinal tract and anaphylaxis in both the prevention and treatment models.

CLINICAL IMPLICATIONS:

IMOs might be suitable candidates for the management of peanut-induced allergy.

• Authors: Fu-Gang Zhu, Ekambar R Kandimalla, Dong Yu, Sudhir Agrawal
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 120 Issue 3 Pg. 631-7 (Sep 2007) ISSN: 0091-6749 [Print] United States
• PMID: 17582479 (Publication Type: Journal Article)

Chemical References

• Immunoglobulin G
• Immunologic Factors
• Interleukin-13
• Interleukin-5
• Oligodeoxyribonucleotides
• Toll-Like Receptor 9
• Immunoglobulin E
• 7-deaza-2'-deoxyguanosine
• Interferon-gamma
• Deoxyguanosine

Topics

• Administration, Oral
• Amino Acid Motifs (immunology)
• Animals
• Deoxyguanosine (administration & dosage, analogs & derivatives, chemical synthesis, immunology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Immunoglobulin E (blood)
• Immunoglobulin G (blood)
• Immunologic Factors (administration & dosage, chemical synthesis, immunology)
• Interferon-gamma (metabolism)
• Interleukin-13 (metabolism)
• Interleukin-5 (metabolism)
• Intestines (drug effects, immunology, pathology)
• Mice
• Oligodeoxyribonucleotides (administration & dosage, chemical synthesis, immunology)
• Peanut Hypersensitivity (prevention & control)
• Spleen (cytology, drug effects, immunology)
• Th1 Cells (drug effects, immunology)
• Th2 Cells (drug effects, immunology)
• Toll-Like Receptor 9 (agonists)