Anti-allergic effects of Lactobacillus crispatus KT-11 strain on ovalbumin-sensitized BALB/c mice

The definitive version is available at www.blackwell-synergy.comIn this study, we investigated the effects of oral ingestion of Lactobacillus crispatus KT-11 strain (KT-11) on the immune response in an allergic rhinitis mouse model, ovalbumin (OVA)-sensitized BALB/c mice. Sneezing activity in mice that were administered a KT-11-supplemented diet was significantly lower than that in mice administered a KT-11-free diet (control diet) at age 11 weeks. We found that serum OVA-specific immunoglobulin E (IgE) levels and total number of interleukin (IL)-4+CD4+ spleen cells in mice that were administered a KT-11-supplemented diet were significantly lower than in mice administered a control diet. The ratio of spleen interferon-gamma+CD4+/IL-4+CD4+ cells was higher in the mice administered the KT-11-supplemented diet compared to that in mice administered the control or L. rhamnosus GG-supplemented diet. In contrast, the number of CD11b+CD80+ and Fc epsilon RI alpha+CD117+ cells was significantly lower in mice administered the KT-11-supplemented diet. These results suggested that KT-11 reduced OVA-induced allergic symptoms in BALB/c mice via the adjustment of the T helper type 1/T helper type 2 balance, and a decrease in the number of antigen-presenting cells and high affinity IgE receptor-positive mast cells.ArticleANIMAL SCIENCE JOURNAL. 81(6):699-705 (2010)journal articl

FcγRIIb Inhibits Allergic Lung Inflammation in a Murine Model of Allergic Asthma

Allergic asthma is characterized by airway eosinophilia, increased mucin production and allergen-specific IgE. Fc gamma receptor IIb (FcγRIIb), an inhibitory IgG receptor, has recently emerged as a negative regulator of allergic diseases like anaphylaxis and allergic rhinitis. However, no studies to date have evaluated its role in allergic asthma. Our main objective was to study the role of FcγRIIb in allergic lung inflammation. We used a murine model of allergic airway inflammation. Inflammation was quantified by BAL inflammatory cells and airway mucin production. FcγRIIb expression was measured by qPCR and flow cytometry and the cytokines were quantified by ELISA. Compared to wild type animals, FcγRIIb deficient mice mount a vigorous allergic lung inflammation characterized by increased bronchoalveolar lavage fluid cellularity, eosinophilia and mucin content upon ragweed extract (RWE) challenge. RWE challenge in sensitized mice upregulated FcγRIIb in the lungs. Disruption of IFN-γ gene abrogated this upregulation. Treatment of naïve mice with the Th1-inducing agent CpG DNA increased FcγRIIb expression in the lungs. Furthermore, treatment of sensitized mice with CpG DNA prior to RWE challenge induced greater upregulation of FcγRIIb than RWE challenge alone. These observations indicated that RWE challenge upregulated FcγRIIb in the lungs by IFN-γ- and Th1-dependent mechanisms. RWE challenge upregulated FcγRIIb on pulmonary CD14+/MHC II+ mononuclear cells and CD11c+ cells. FcγRIIb deficient mice also exhibited an exaggerated RWE-specific IgE response upon sensitization when compared to wild type mice. We propose that FcγRIIb physiologically regulates allergic airway inflammation by two mechanisms: 1) allergen challenge mediates upregulation of FcγRIIb on pulmonary CD14+/MHC II+ mononuclear cells and CD11c+ cells by an IFN-γ dependent mechanism; and 2) by attenuating the allergen specific IgE response during sensitization. Thus, stimulating FcγRIIb may be a therapeutic strategy in allergic airway disorders

LAT Is Essential for FcεRI-Mediated Mast Cell Activation

AbstractThe linker molecule LAT is a substrate of the tyrosine kinases activated following TCR engagement of T cells. LAT is also expressed in platelets, NK, and mast cells. Although LAT-deficient mice contain normal numbers of mast cells, we found that LAT-deficient mice were resistant to IgE-mediated passive systemic anaphylaxis. LAT-deficient bone marrow–derived mast cells (BMMC) showed normal growth and development. Whereas tyrosine phosphorylation of FcεRI, Syk, and Vav was intact in LAT-deficient BMMCs following FcεRI engagement, tyrosine phosphorylation of SLP-76, PLC-γ1, and PLC-γ2 and calcium mobilization were dramatically reduced. LAT-deficient BMMCs also exhibited profound defects in activation of MAPK, degranulation, and cytokine production after FcεRI cross-linking. These results show that LAT plays a critical role in FcεRI-mediated signaling in mast cells

Scrub Typhus Vaccine Candidate Kp r56 Induces Humoral and Cellular Immune Responses in Cynomolgus Monkeys

A truncated recombinant 56-kDa outer membrane protein of the Karp strain of Orientia tsutsugamushi (Kp r56) was evaluated in cynomolgus monkeys (Macaca fascicularis) for immunogenicity and safety as a vaccine candidate for the prevention of scrub typhus. This recombinant antigen induced strong humoral and cellular immune responses in two monkeys and was found to be well tolerated. Antigen-specific immunoglobulin M (IgM) and IgG were produced to almost maximal levels within 1 week of a single immunization. Peripheral blood mononuclear cells from vaccinated animals showed an induction of antigen-specific proliferation and gamma interferon production. The Kp r56 was not as efficient as infection with live organisms in preventing reinfection but was able to reduce the inflammation produced at the site of challenge. This report describes the results of the first systematic study of the immunogenicity of a recombinant scrub typhus vaccine candidate in a nonhuman primate model