ABSTRACT
Lipopolysaccharide (LPS) is a major component of environmental microbial products. Studies have defined the LPS dose as a critical determining factor in driving differential T-cell polarization but the direct effects of LPS on individual antigen-presenting cells is unknown. Here, we investigated the effects of LPS doses on naive B cells and the subsequent modulatory effects of these LPS-activated B cells on T-cell polarization. The LPS was able to induce a proliferative response starting at a dose of 100 ng/ml and was capable of enhancing antigen internalization at a dose of 1 microg/ml in naive B cells. Following LPS stimulation, up-regulation of the surface markers CD40, CD86, I-Ad, immunoglobulin M, CD54 and interleukin-10 production, accompanied by down-regulation of CD5 and CD184 (CXCR4) were observed in a LPS dose-dependent manner. Low doses (<10 ng/ml) of LPS-activated B cells drove T helper type 2 polarization whereas high doses (>0.1 microg/ml) of LPS-activated B cells resulted in T regulatory type 1 cell polarization. In conclusion, LPS-activated B cells acquire differential modulatory effects on T-cell polarization. Such modulatory effects of B cells are dependent on the stimulation with LPS in a dose-dependent manner. These observations may provide one of the mechanistic explanations for the influence of environmental microbes on the development of allergic diseases.
Subject(s)
B-Lymphocytes/immunology , Lipopolysaccharides/immunology , Lymphocyte Cooperation/immunology , T-Lymphocytes/immunology , Animals , Antigens, Surface/metabolism , Cell Polarity/immunology , Cell Proliferation , Cells, Cultured , Dose-Response Relationship, Immunologic , Endocytosis/immunology , Interleukin-10/biosynthesis , Lectins, C-Type/immunology , Lymphocyte Activation/immunology , Mannose Receptor , Mannose-Binding Lectins/immunology , Mice , Mice, Inbred BALB C , Mice, Transgenic , Pinocytosis , Receptors, Cell Surface/immunology , Spleen/immunology , Up-Regulation/immunologyABSTRACT
Blomia tropicalis allergens are the most important mite allergens in tropical regions. Most of them only have 30-40% sequence identity with their Dermatophagoides counterparts and they share low IgE cross reactivity and exhibit different immunobiology. Unlike the pyroglyphid counterparts, Blo t 5 is the major allergen whereas Blo t 1 only has modest allergenicity.
Subject(s)
Allergens/chemistry , Mites/chemistry , Allergens/immunology , Amino Acid Sequence , Animals , Antigens, Dermatophagoides/chemistry , Antigens, Dermatophagoides/immunology , Antigens, Plant , Arthropod Proteins , Cysteine Endopeptidases/chemistry , Humans , Hydrogen-Ion Concentration , Hypersensitivity, Immediate/immunology , Immunoglobulin E/immunology , Molecular Sequence Data , Sequence Alignment , Serine EndopeptidasesABSTRACT
1. Allergic diseases are characterized by inappropriate immune responses to common environmental antigens. The prevalence of these diseases has been increasing worldwide for reasons that are not exactly clear. 2. Current treatment is largely symptomatic. Because the initial observation that simple plasmid DNA injections resulted in in vivo protein expression and induction of adaptive immune responses to the encoded antigen, the potential of modifying the allergic immune responses by DNA vaccination so as to treat and prevent these diseases has been explored extensively. 3. In the present paper we review preclinical studies using animal models of allergic diseases, with an emphasis on DNA vaccine design, for house dust mite allergens-related allergic asthma.
