Production of Salivary Immunoglobulin A and Suppression of <i>Dermatophagoides pteronyssinus</i>-Induced Airway Inflammation by Local Nasal Immunotherapy

Abstract

Background: Local nasal immunotherapy (LNIT) is an effective immunotherapeutic modality, especially when targeting a single immunodominant peptide from an allergen. However, the working mechanisms of LNIT are poorly understood. We hypothesized that LNIT with a mixture of group 2 allergens of Dermatophagoides pteronyssinus (Der p 2) protein and fungal immunomodulatory peptide (FIP) would generate suppression of Der p-induced airway inflammation through immunoglobulin (Ig) A secretion in the airways. Method: Mice were sensitized with recombinant Der p 2 (rDer p 2) and Der p followed by LNIT with rDer p 2 in conjunction with FIP. After intratracheal challenge with rDer p 2 and Der p, the airway inflammation was determined by analyzing the cell subpopulation and cytokine concentration in the bronchoalveolar lavage fluid. The allergen-specific IgE, IgG2a and IgG in the sera and IgA in the saliva were measured by ELISA. Results: LNIT with rDer p 2 in conjunction with FIP could downregulate the lymphocyte infiltration in both rDer p 2- and Der p-induced airway inflammation. Both total and specific IgA in the saliva were increased after LNIT. Serum levels of IL-4, IL-10 and specific IgE were reduced and the specific IgG2a and IgG increased after LNIT. After LNIT, there was a reduction of airway hypersensitivity at 30 min after allergen challenge in the rDer p 2-and Der p-sensitized mice, with a significant decrease only in rDer p 2-sensitized mice. Conclusion: LNIT with rDer p 2 in conjunction with FIP was not only able to suppress rDer p 2-induced airway inflammation but also generate suppression of Der p-induced airway inflammation. The simultaneous reduction of IL-4 and IL-10 indicated that IL-10-producing cells were not activated by LNIT. The increment of IgA in the airway might play a role in the prevention of airway inflammation.

Effects of local nasal immunotherapy in allergic airway inflammation: Using urea denaturedDermatophagoides pteronyssinus

“…4,16 According to our previous animal model and other reports, IgE was elevated in mice sera before allergen sensitization and was decreased after treatment. 8,17 Similar findings were observed after LNIT with DNDp. Significantly, decreased Der p-specific IgE may be due to decreased production of IL-4 in Th2 cells.…”

“…8 Briefly, aerosol was generated by placing 200 ul of saline or different doses of methacholine (0, 12.5, 25, and 50 mg/ml; Sigma) solution in the cup of an ultrasonic nebulizer. It was delivered via a connecting tube and a 3-way connector to the animal chamber of the plethysmograph.…”

“…5,6 The secretion of local salivary IgA and systemic serum IgG2a was up-regulated after LNIT in a mouse asthma model. 7,8 Our previous study showed that LNIT with Dermatophagoides pteronyssinus (Der p)-coated strips was effective for treating patients with allergic rhinitis and Der p allergy after LNIT. 3 Der p-specific IgE and IgG1 can down-regulate and up-regulate Der p-specific IgG4 in the sera.…”

Characterization of an immunomodulatory Der p 2-FIP-fve fusion protein produced in transformed rice suspension cell culture

“…Treg cells were observed from stimulating PBMCs of Dermatophagoides farinaesensitized allergic rhinitis patients with a peptide containing the N-terminal 63 residues of Der f 2 in combination with Fve ). Furthermore, in a mouse model for local nasal immunotherapy, Der p 2-sensitized mice treated with either Der p 2 peptide or Der p 2 plus Fve could downregulate not only Der p 2-specific IgE and Th2 immune responses but also Der p 2-induced airway inflammation and airway hypersensitivity (Liu et al 2003;Liu and Tsai 2005). These results suggested that Fve could execute its immunomodulatory function on the established adaptive immunity by enhancing the number and the function of allergen-specific Treg cells, possibly via its potent activity in stimulating IFN-c production.…”

“…Fve was able to induce mitogenic proliferation of human peripheral mononuclear cells (PBMCs) and enhance mRNA transcription of interleukin (IL)-2 and interferon (IFN)-c in vitro (Ko et al 1995;Wang et al 2004). Administration of Fve with allergens either intraperitoneally, orally, or intranasally inhibited allergeninduced systemic anaphylactic responses (Ko et al 1995), food allergic reactions (Hsieh et al 2003), or allergic airway inflammation (Liu et al 2003;Liu and Tsai 2005;Hsieh et al 2007) in vivo, respectively. Recently, Fve has also been shown to exhibit potent adjuvant properties that enhanced the immunogenicity of the human papillomavirus type-16 (HPV-16) E7 oncoprotein and conferred increased antitumor effects against the inoculation of HPV-16 E7-expressing TC-1 cells in a mouse model (Ding et al 2009).…”