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


CONCLUSIONS
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.


CONCLUSIONS
IMOs might be suitable candidates for the management of peanut-induced allergy.
Zhu
Fu-Gang
FG
Idera Pharmaceuticals, Inc, Cambridge, Mass, USA.
Kandimalla
Ekambar R
ER
Yu
Dong
D
Agrawal
Sudhir
S
D000284:Administration, Oral; D020816:Amino Acid Motifs / Q000276:immunology; D000818:Animals; D003849:Deoxyguanosine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000276:immunology; D021183:Peanut Hypersensitivity / Q000517:prevention & control*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000819:agonists*
D007074:Immunoglobulin G; D007155:Immunologic Factors; D018793:Interleukin-13; D015848:Interleukin-5; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9; D007073:Immunoglobulin E; C045550:7-deaza-2'-deoxyguanosine; D007371:Interferon-gamma; D003849:Deoxyguanosine