Modulation of Airway Inflammation by Immunostimulatory CpG Oligodeoxynucleotides in a Murine Model of Allergic Aspergillosis

Abstract

Allergic aspergillosis is a Th2 T-lymphocyte-mediated pulmonary complication in patients with atopic asthma and cystic fibrosis. Therefore, any therapeutic strategy that selectively inhibits Th2 T-cell activation may be useful in downregulating allergic lung inflammation in asthma. In the present study, we developed a CpG oligodeoxynucleotide (ODN)-based immune intervention of allergic inflammation in a mouse model of allergic aspergillosis. Four different groups of mice were used in a short-term immunization protocol. Three experimental groups of animals (groups 1 to 3) were sensitized with Aspergillus fumigatus antigens. Animals in group 1 were immunized with A. fumigatus antigen alone, while those in group 2 were treated with CpG-ODN 1 day before the first antigen immunization, and the animals in group 3 received the first CpG-ODN administration between the antigen treatments. The animals in group 4 served as controls and were given phosphate-buffered saline. Allergen-specific serum immunoglobulins and total immunoglobulin E in different groups of animals were measured by enzyme-linked immunosorbent assay, while airway remodeling and cytokine production were studied by immunohistochemistry. The results demonstrated that CpG-ODN administration either before (group 2) or between (group 3) antigen treatments resulted in reduced total immunoglobulin E levels and peripheral blood eosinophil numbers compared to A. fumigatus allergen-sensitized group 1 animals. Similarly, treatment with CpG-ODN also downregulated inflammatory cell infiltration, goblet cell hyperplasia, and basement membrane thickening compared to A. fumigatus-sensitized mice. The distinct reduction in peripheral blood eosinophilia and airway remodeling in CpG-ODN-treated mice emphasized its usefulness as an immunomodulating agent for allergic fungal diseases.

Co-encapsulation of an antigen and CpG oligonucleotides into PLGA microparticles by TROMS technology

“…The ability of CpG ODN to trigger the production of T-helper 1 and proinflammatory cytokines and IFN-dependent IgG2a antibodies has been observed with a variety of co-administered antigens [50][51][52][53]. This adjuvant effect was clearly dose dependent and mediated by cytokines produced following stimulation of APC, as for example, IL-12.…”

Imprinted DC mediate the immune‐educating effect of early‐life microbial exposure

“…Although numerous reported epidemiological and experimental studies have demonstrated the inhibitory role of live or killed microbes or microbial components on allergic responses [18][19][20][21][22][23][24][25], the basis for this inhibition remains unclear. In particular, little experimental study has been performed on the effect and mechanism of neonatal microbial exposure on airway allergic inflammation.…”

IL-33 Exacerbates Eosinophil-Mediated Airway Inflammation

“…After 24 h, the cells were stained with allophycocyanin-conjugated anti-CCR3 Ab. Cytospins were prepared from some cultures and stained in the presence of potassium cyanide for eosinophil peroxidase (EPO; exclusive to eosinophils), according to a protocol published previously (36), or with H&E.…”