Dietary medium-chain triglycerides promote oral allergic sensitization and orally induced anaphylaxis to peanut protein in mice Jianing Li, MS, Yu Wang,

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Presentation transcript:

Dietary medium-chain triglycerides promote oral allergic sensitization and orally induced anaphylaxis to peanut protein in mice Jianing Li, MS, Yu Wang, BS, Lihua Tang, PhD, Willem J.S. de Villiers, MD, PhD, Donald Cohen, PhD, Jerold Woodward, PhD, Fred D. Finkelman, MD, Erik R.M. Eckhardt, PhD Journal of Allergy and Clinical Immunology Volume 131, Issue 2, Pages 442-450 (February 2013) DOI: 10.1016/j.jaci.2012.10.011 Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Effects of triglycerides on antigen absorption. A, Plasma iodine 125 levels 30 minutes after gavage of radiolabeled peanut protein with indicated vehicles (n = 6). B, PL81 blocks LCT absorption, as reflected by increased buoyancy because of lipid entrapment. Tissue was obtained 5 hours after gavage. C and D, CD11c+ and DQ-OVA+ cells in Peyer patches 16 hours after DQ-OVA gavage in indicated vehicles (n = 4). Journal of Allergy and Clinical Immunology 2013 131, 442-450DOI: (10.1016/j.jaci.2012.10.011) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 MCT causes allergic sensitization. A-C, Anti-peanut antibodies 18 days after gavage with peanut protein (80 mg) in indicated vehicles (n = 6). The LCT was peanut oil in Fig 2, A and B, and soybean oil in Fig 2, C. D, Splenocyte IL-13 release (n = 4). ∗P < .05. E, Gavage of peanut protein in the LCT (OT) 1 week before gavage with the MCT induces oral tolerance (n = 6). F, Anti-OVA IgE levels 18 days after gavage with OVA (60 mg) in indicated vehicles (n = 6). Journal of Allergy and Clinical Immunology 2013 131, 442-450DOI: (10.1016/j.jaci.2012.10.011) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Tslp mRNA in epithelial cells of the jejunum 5 hours after gavage of 0.2 mL of the MCT, the LCT, or saline (A) or 0.2 mL of the LCT, the LCT plus PL81, or saline plus PL81 (B; n = 6). Journal of Allergy and Clinical Immunology 2013 131, 442-450DOI: (10.1016/j.jaci.2012.10.011) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Effect of MCT feeding on intestinal epithelial TH2 cytokine expression. A, TSLP mRNA in epithelia from indicated sections 3 weeks after feeding (n = 5). B, IL-25 and IL-33 mRNA in jejunal epithelial cells 3 weeks after feeding (n = 5). C, IgE against peanut protein during 4 weeks of feeding with diets enriched with peanut flour (n = 6). Journal of Allergy and Clinical Immunology 2013 131, 442-450DOI: (10.1016/j.jaci.2012.10.011) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Promotion of TH2 responses by dietary MCTs. DO11.10 mice were fed MCT- or LCT-based diets containing egg white (MCT+egg and LCT+egg) or without egg white (MCT and LCT; n = 5 per group). One week later, splenocytes were stimulated ex vivo with OVA peptide, and indicated cytokines were measured by using an ELISA. Journal of Allergy and Clinical Immunology 2013 131, 442-450DOI: (10.1016/j.jaci.2012.10.011) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 IgG-dependent anaphylaxis upon systemic challenge. Mice were gavaged once with peanut butter protein in indicated vehicles and then challenged by means of intraperitoneal injection 18 days later (n = 6). A-C, Parameters included plasma mouse mast cell protease 1 (mmcp-1) 90 minutes after the challenge (Fig 6, A), body temperature (Fig 6, B), and clinical score (Fig 6, C). D, Pretreatment with blocking antibodies against IgG receptors (2.4G2) but not against IgE (EM-95) blunted anaphylaxis. Journal of Allergy and Clinical Immunology 2013 131, 442-450DOI: (10.1016/j.jaci.2012.10.011) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 7 IgE-dependent orally induced anaphylaxis is aggravated by MCTs. A, Body temperature of mice (n = 6-7) challenged with peanut protein in the MCT with or without pretreatment with IgE blocking antibody. Sensitization occurred by means of gavage on days 1 and 8, and challenges were performed on day 48. B, Mice (n = 6) were sensitized as in Fig 7, A, but the oral challenge was performed by using gavage of peanut protein in different vehicles. C, Plasma mouse mast cell protease 1 (mmcp-1) levels in mice in Fig 7, B. D, Inhibition of basophil activation by including Intralipid (2 different dilutions) with OVA added to sensitized basophils (n = 4 per group). E, BALB/c mice (n = 9 per group) were sensitized intraperitoneally with OVA in alum and then challenged with 60 mg of OVA by means of gavage in the indicated vehicle. All experiments were repeated at least twice with similar outcome, except those shown in Fig 7, B and C, which were performed once. Journal of Allergy and Clinical Immunology 2013 131, 442-450DOI: (10.1016/j.jaci.2012.10.011) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions