title: Genetically engineered Lactococcus lactis protect against house dust mite allergy in a BALB/c mouse model.
abstract: BACKGROUND
  Mucosal vaccine based on lactic acid bacteria is an attractive concept for the prevention and treatment of allergic diseases, but their mechanisms of action in vivo are poorly understood. Therefore, we sought to investigate how recombinant major dust mite allergen Der p2-expressing Lactococcus lactis as a mucosal vaccine induced the immune tolerance against house dust mite allergy in a mouse model.
  
  
  METHODS
  Three strains of recombinant L. lactis producing Der p2 in different cell components (extracellular, intracellular and cell wall) were firstly constructed. Their prophylactic potential was evaluated in a Der p2-sensitised mouse model, and immunomodulation properties at the cellular level were determined by measuring cytokine production in vitro.
  
  
  RESULTS
  Der p2 expressed in the different recombinant L. lactis strains was recognized by a polyclonal anti-Der p2 antibody. Oral treatment with the recombinant L. lactis prior sensitization significantly prevented the development of airway inflammation in the Der p2-sensitized mice, as determined by the attenuation of inflammatory cells infiltration in the lung tissues and decrease of Th2 cytokines IL-4 and IL-5 levels in bronchoalveolar lavage. In addition, the serum allergen-specific IgE levels were significantly reduced, and the levels of IL-4 in the spleen and mesenteric lymph nodes cell cultures were also markedly decreased upon allergen stimulation in the mice fed with the recombinant L. lactis strains. These protective effects correlated with a significant up-regulation of regulatory T cells in the mesenteric lymph nodes.
  
  
  CONCLUSIONS
  Oral pretreatment with live recombinant L. lactis prevented the development of allergen-induced airway inflammation primarily by the induction of specific mucosal immune tolerance.
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R. China.
authors.forename: Chunqing
authors.initials: C
authors.lastname: Ai
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R. China.
authors.forename: Qiuxiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R. China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R. China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R. China.
authors.forename: Fengwei
authors.initials: F
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R. China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R. China; Synergistic Innovation Center for Food Safety and Nutrition, Jiangnan University, Wuxi, Jiangsu, P. R. China.
authors.forename: Yong Q
authors.initials: YQ
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R. China; Synergistic Innovation Center for Food Safety and Nutrition, Jiangnan University, Wuxi, Jiangsu, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000906:Antibodies; D039741:Antigens, Dermatophagoides / Q000096:biosynthesis / Q000276:immunology*; D060829:Arthropod Proteins / Q000096:biosynthesis / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D060846:Cell Engineering / Q000379:methods; D002473:Cell Wall / Q000235:genetics / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects; D018928:Immunity, Mucosal / Q000187:drug effects*; D007073:Immunoglobulin E / Q000096:biosynthesis; D056747:Immunomodulation; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015848:Interleukin-5 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013294:Lactococcus lactis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019936:Probiotics / Q000494:pharmacology*; D039981:Pyroglyphidae / Q000737:chemistry / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D000906:Antibodies; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C451163:Dermatophagoides pteronyssinus antigen p 2; D015848:Interleukin-5; D014612:Vaccines; D015847:Interleukin-4; D007073:Immunoglobulin E