Oral administration of CpG-ODNs suppresses antigen-induced asthma in mice

Abstract

SummaryOligodeoxynucleotides containing CpG motifs (CpG-ODNs) can protect against eosinophilic airway inflammation in asthma. Previously we have found that parenteral or mucosal administration of CpG-ODNs is effective in preventing (as well as reversing established) disease. In this study, we examined the effect of oral CpG-ODNs on the development of immune tolerance. Using an ovalbumin (OVA)-induced murine model of asthma, we found that CpG-ODNs, administered orally around the time of sensitization, prevented eosinophilic airway inflammation in a dose-dependent manner. Although oral co-administration of CpG-ODNs with OVA (known to induce tolerance) did not significantly change the inhibition of OVA-induced airway eosinophilia, it did modulate OVA-specific immunoglobulin responses: oral administration of OVA alone suppressed OVA-specific IgG1 production, but only mice that received CpG-ODNs demonstrated enhanced levels of OVA-specific IgG2c. Finally, we examined whether oral administration of CpG-ODNs, alone or with OVA, could reverse established eosinophilic airway inflammation. Again, neither OVA nor CpG-ODNs alone modulated established eosinophilic airway inflammation, but a combination of the OVA and CpG-ODNs successfully desensitized the mice. This desensitization was associated with suppression of OVA-specific IgE and enhancement of OVA-specific IgG2c production. These findings provide the first indication that oral administration of CpG-ODNs is effective in preventing and reversing antigen-induced eosinophilic airway inflammation. CpG-ODNs may be useful as a component of oral immunotherapy to promote tolerance in established asthma.

Fetal Epigenetic Mechanisms and Innate Immunity in Asthma

“…Moreover, when administered in combination with an experimental allergen, CpG promotes the reversal of established eosinophilic inflammation [41]. We recently found that TLR3 or TLR7 activation by viral TLR ligands has both preventive and suppressive effects on experimental asthma that are mediated by the additive effects of IL-12 and IL-10; however, this concept was not proven in a prenatal experimental set-up [42].…”

“…Kitagaki et al [41] demonstrated that application of TLR9 ligand CpG DNA prior to sensitization prevents Th2 inflammatory responses and effectively interacts with the development of atopic airway diseases in a murine model of experimental asthma. Moreover, when administered in combination with an experimental allergen, CpG promotes the reversal of established eosinophilic inflammation [41].…”

Lung Microbiome for Clinicians. New Discoveries about Bugs in Healthy and Diseased Lungs

“…The presence of H. pylori in the stomach is associated with decreased intestinal microbiome diversity, which is also associated with increased risk for allergic rhinitis and peripheral blood eosinophilia (61). Lessons from animal models show that disruption of the gastrointestinal microbiota may lead to abnormal immune responses (62)(63)(64)(65)(66). …”

A Brave New World: The Lung Microbiota in an Era of Change

“…In mice, disruption of the gastrointestinal microbiota leads to abnormal airway allergic responses (41,42). In other mouse models, oral ingestion of various strains of Lactobacillus and ingestion of bacterial STATE OF THE ART products modulate allergic pulmonary inflammation (43)(44)(45). More importantly, there is evidence that children whose stomach is colonized with Helicobacter pylori are 40-60% less likely to have childhood-onset asthma than children who are not carriers (46).…”