Abstract
CpG-oligodeoxynucleotides (CpG-ODNs) constitute an attractive alternative for asthma treatment. However, very little evidence is available from studies on the oral administration of CpG-ODNs in animals. Previously, we developed acid-resistant particles (named ODNcap) as an oral delivery device for ODNs. Here, we showed that free feeding of an ODNcap-containing feed prophylactically attenuates allergic airway inflammation, hyperresponsiveness, and goblet cell hyperplasia in an ovalbumin-induced asthma model. Using transcriptomics-driven approaches, we demonstrated that injury of pulmonary vein cardiomyocytes accompanies allergen inhalation challenge, but is inhibited by ODNcap feeding. We also showed the participation of an airway antimicrobial peptide (Reg3γ) and fecal microbiota in the ODNcap-mediated effects. Collectively, our findings suggest that daily oral ingestion of ODNcap may provide preventive effects on allergic bronchopulmonary insults via regulation of mechanisms involved in the gut-lung connection.
Highlights
Asthma is a respiratory syndrome characterized by airway hyperresponsiveness (AHR), inflammation, and remodeling [1]
Th2 cytokines in bronchoalveolar lavage fluid (BALF) accumulated to significantly higher levels in Ctrl-F and Cap-F compared to NT, whereas the levels of these cytokines were comparable between NT and ODNcap-F (Figure 2C)
OVA-specific immunoglobulin G1 (IgG1) was detected in the serum and BALF of OVAsensitized/challenged mice, while the level of these antibodies was significantly reduced in ODNcap-F compared to Ctrl-F and Cap-F (Figure 2E)
Summary
Asthma is a respiratory syndrome characterized by airway hyperresponsiveness (AHR), inflammation, and remodeling [1]. Adequate exposure to bacterial components such as endotoxins and DNA through pattern recognition receptors (PRRs) may reduce the risk of atopy and asthma development in childhood by activating host innate immunity [4, 5]. Based on this idea (the hygiene hypothesis), asthma therapeutics targeting Toll-like receptors (TLRs), a kind of PRR, have been investigated [6].
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