Sublingual Immunotherapy with Sal k1 Expressing Lactococcus lactis Down-regulates Th2 Immune Responses in Balb/c Mice

Iran J Allergy Asthma Immunol. 2018 Jun;17(3):281-290.

Abstract

Sublingual immunotherapy (SLIT) has been introduced as a noninvasive and safer approach for allergen-specific immunotherapies. In this study we investigated the efficacy of oral immunotherapy with recombinant Salsola kali 1 protein (Sal k 1) on Th1/Th2 balance in a mouse model of allergy. Female Balb/c mice were intraperitoneally sensitized with rSal k1, followed by a respiratory challenge with 1% (w/v) rSal k1. The sensitized mice were subjected to SLIT using rSal K1 expressing Lactobacillus lactis strain for three weeks. Each week the experimental group underwent SLIT protocol twice. Finally, serum levels of specific immunoglobulins including IgE, IgG1 and IgG2a, as well as secretion of different cytokines from splenocytes including IL-2, IL-4, IL-10, IFNγ and TGFβ into culture media were measured by ELISA. Following immunotherapy, the levels of specific IgE and IgG1 in mice sera as well as IL-4 level in supernatant of splenocytes were significantly lower than allergic controls. While serum IgG2a, IgG2a/IgG1 ratio as well as concentration of IL-2, IL-10, IFNγ, and TGFβ were higher in the SLIT group compared to the controls. The histopathological examination of intestinal tissues revealed no sign of inflammatory response following SLIT. This study revealed that Th2 immune responses are reduced in allergic mice after feeding them with allergen expressing probiotic bacteria as a SLIT approach. Since the safety of this procedure was previously approved, thus, it seems that a similar protocol using human based probiotics could be applied for Salsola kali sensitive patients.

Keywords: Lactococcus lactis; Salsola kali; Sublingual immunotherapy.

MeSH terms

  • Allergens / genetics
  • Allergens / immunology*
  • Animals
  • Antigens, Plant / genetics
  • Antigens, Plant / immunology*
  • Cells, Cultured
  • Cytokines / metabolism
  • Disease Models, Animal
  • Down-Regulation
  • Female
  • Humans
  • Hypersensitivity / immunology
  • Hypersensitivity / therapy*
  • Immunoglobulin E / blood
  • Lactococcus lactis / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Salsola / immunology
  • Sublingual Immunotherapy / methods*
  • Th2 Cells / immunology
  • Transgenes / genetics

Substances

  • Allergens
  • Antigens, Plant
  • Cytokines
  • Sal k 5 allergen, Salsola kali
  • Immunoglobulin E