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Virus-specific IgE enhances airway responsiveness on reinfection with respiratory syncytial virus in newborn mice  Azzeddine Dakhama, PhD, Young-Mok Lee,

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Presentation on theme: "Virus-specific IgE enhances airway responsiveness on reinfection with respiratory syncytial virus in newborn mice  Azzeddine Dakhama, PhD, Young-Mok Lee,"— Presentation transcript:

1 Virus-specific IgE enhances airway responsiveness on reinfection with respiratory syncytial virus in newborn mice  Azzeddine Dakhama, PhD, Young-Mok Lee, MD, PhD, Hiroshi Ohnishi, MD, PhD, Xia Jing, BS, Annette Balhorn, BS, Katsuyuki Takeda, MD, PhD, Erwin W. Gelfand, MD  Journal of Allergy and Clinical Immunology  Volume 123, Issue 1, Pages e5 (January 2009) DOI: /j.jaci Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Timing of RSV infection and administration of anti-IgE treatment in the passive IgE sensitization model and neonatal RSV infection model. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Effect of anti-IgE on airway responsiveness in the passive sensitization model. Adult mice were infected with RSV and passively sensitized with RSV-IgE or OVA-IgE, with or without treatment with anti-IgE or control rat IgG1. Airway responsiveness to methacholine (A and B), lung viral titers (C), BAL IFN-γ levels (D), and in vitro IFN-γ production by PBLN cells (E) were assessed on day 6 after infection. M2P, H-2Kd-restricted RSV M2 peptide82-90; MCh, methacholine; Med, culture medium; PFU, plaque-forming units. Data are means ± SEMs of n = 8 mice in each group. ∗Significant difference between the groups, P < .05. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Role of IL-4/IL-13 and FcɛRI in the development of enhanced airway responsiveness on reinfection of mice initially infected as newborns with RSV. Wild-type mice (WT), mice lacking both IL-4 and IL-13 genes (IL-4−/−/IL-13−/−), and FcɛRI-deficient mice (FcɛRI−/−) were initially infected with RSV as newborns and were reinfected 5 weeks later. Airway responsiveness (A), BAL cellularity and airway goblet cell metaplasia (Table II), BAL cytokine levels (B), and in vitro cytokine production (Fig E3) were assessed on day 6 after reinfection. BALF, BAL fluid; MCh, Methacholine. Data are means ± SEMs of n = 6 mice in each group. ∗Significant difference between the groups, P < .05. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Effect of mast cell transfer on the development of enhanced airway responsiveness on reinfection of newborn FcɛRI−/− mice. FcɛRI−/− mice were initially infected with RSV as newborns and were reinfected 5 weeks later. Mast cells, derived from bone marrow of donor wild type (wt-MC) mice or FcɛRI−/−(KO-MC) mice, were adoptively transferred into recipient FcɛRI−/− mice 2 weeks after the primary neonatal RSV infection. Airway responsiveness to methacholine (MCh)(A), BAL cellularity (B), airway goblet cell metaplasia (C), and BAL cytokine levels (D) was assessed on day 6 after reinfection. Data are means ± SEMs of n = 6 mice in each group. BM, Basement membrane; Tot, total cells; Eos, eosinophils; Lym, lymphocytes; Mac, macrophages; Neu, neutrophils. ∗Significant difference compared with all other groups, P < .05. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Effect of anti-IgE treatment on the development of enhanced airway responsiveness on reinfection of WT newborn mice with RSV. Mice were initially infected with RSV as newborns and were reinfected 5 weeks later. Treatment with anti-IgE or control rat IgG1 antibody was administered beginning the week of initial infection and was maintained until reinfection. Airway responsiveness (A), BAL cellularity (B), airway goblet cell metaplasia (C), BAL cytokine levels (D), and in vitro cytokine production (Fig E4) were assessed on day 6 after reinfection. Data are means ± SEMs of n = 8 mice in each group. BM, Basement membrane; Tot, total cells; Eos, eosinophils; Lym, lymphocytes; Mac, macrophages; Neu, neutrophils. ∗Significant difference between the groups, P < .05. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Effect of anti-IgE on IgE binding and mast cell degranulation in vitro
Effect of anti-IgE on IgE binding and mast cell degranulation in vitro. A, Mast cells were sensitized with RSV-IgE and incubated with RSV (Control), anti-IgE, or control rat IgG1 (2000 ng/mL). B, Effect of anti-IgE on RSV-induced, IgE-mediated mast cell degranulation. C, Effect of anti-IgE on IgE binding on the surface of mast cells. Mast cells were incubated with RSV-IgE (200 ng/106 cells/mL) in the presence of anti-IgE or control rat IgG1 (500 ng/mL). Data are representative of 3 independent experiments with similar results. ∗Significant difference compared with control (RSV-induced degranulation), P < .01. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Kinetics of appearance of serum RSV-specific IgE response
Kinetics of appearance of serum RSV-specific IgE response. After neonatal RSV infection, RSV-specific IgE was detected in the serum of wild-type (WT) mice but not in the serum of mice lacking IL-4 and IL-13 genes (IL-4−/−/IL-13−/−). Data are means ± SEMs of n = 6 mice in each group. ∗Significant difference compared with day 7, P < .05. #Significant difference compared with day 14, P < .01. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 Cytokine production from PBLN cells of wild-type (WT), IL-4−/−/IL-13−/−, and FcɛRI−/− mice. Wild-type (WT) mice, mice lacking IL-4 and IL-13 genes (IL-4−/−/IL-13−/−), and mice lacking the high-affinity receptor for IgE (FcɛRI−/−). Data are means ± SEMs of n = 6 mice in each group. ∗Significant difference between the groups, P < Med, Culture medium. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

10 Cytokine production from wild-type PBLN cells after in vivo treatment with anti-IgE or control rat IgG1. Data are means ± SEMs of n = 8 mice in each group, ∗P < .05. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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