Histamine receptor 2 is a key influence in immune responses to intestinal histamine- secreting microbes Ruth Ferstl, PhD, Remo Frei, PhD, Elisa Schiavi,

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Presentation transcript:

Histamine receptor 2 is a key influence in immune responses to intestinal histamine- secreting microbes Ruth Ferstl, PhD, Remo Frei, PhD, Elisa Schiavi, PhD, Patrycja Konieczna, PhD, Weronika Barcik, MSc, Mario Ziegler, Dipl-Ing, Roger P. Lauener, MD, Christophe Chassard, PhD, Christophe Lacroix, PhD, Cezmi A. Akdis, MD, Liam O'Mahony, PhD Journal of Allergy and Clinical Immunology Volume 134, Issue 3, Pages 744-746.e3 (September 2014) DOI: 10.1016/j.jaci.2014.04.034 Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Histamine from Lactobacillus saerimneri 30a is biologically active. A, L saerimneri 30a culture supernatants significantly reduced LPS-induced NF-κB activation, which was attenuated by blocking the H2R with famotidine. Supernatant from Lactobacillus reuteri (which does not secrete histamine) increased LPS-induced NF-κB activation. *P < .05 compared with LPS alone. Results are expressed as mean ± SD for 3 separate experiments. B, HPLC analysis revealed high levels of histamine and cadaverine in supernatants from L saerimneri 30a cultures. Journal of Allergy and Clinical Immunology 2014 134, 744-746.e3DOI: (10.1016/j.jaci.2014.04.034) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Lactobacillus saerimneri 30a modulates mucosal immune responses via the H2R. Mice (n = 6 per group) received L saerimneri 30a daily for 6 days by oral gavage (1 × 109 cfu/mL). Animals exhibited significant weight loss (A) associated with signs of deteriorating health (B), which was significantly worse in the H2R-deficient animals than in wild-type controls at day 6 (*P < .05 between groups). C, In vitro cytokine secretion from resected PPs was measured after PMA and ionomycin stimulation. L saerimneri 30a administration was associated with the suppression of IL-17 and IFN-γ secretion in wild-type mice. In contrast, IL-4, IL-6, and IL-17 secretion was significantly increased in H2R-deficient animals (*P < .05; **P < .01). PMA, Phorbol 12-myristate 13-acetate. Journal of Allergy and Clinical Immunology 2014 134, 744-746.e3DOI: (10.1016/j.jaci.2014.04.034) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 The H2R antagonist famotidine enhances the detrimental effects of L saerimneri 30a. Mice (n = 8 per group) received L saerimneri 30a daily for 6 days by oral gavage (1 × 109 cfu/mL). Animals exhibited significant weight loss (A) associated with signs of deteriorating health (B), which was significantly worse in the famotidine-treated animals than in controls (*P < .05 between groups). C, In vitro cytokine secretion from mucosal cells was measured after PMA and ionomycin stimulation. L saerimneri 30a administration was associated with the suppression of IL-17; however, the secretion of IL-17 was enhanced in famotidine-treated animals. PMA, Phorbol 12-myristate 13-acetate. Journal of Allergy and Clinical Immunology 2014 134, 744-746.e3DOI: (10.1016/j.jaci.2014.04.034) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 CD4+ lymphocyte cytokine response to L saerimneri 30a. Intracellular staining of IL-17+ and IFN-γ+ CD4 lymphocytes was performed for PP (A) and mesenteric lymph nodes (B). The percentage of IL-17+ lymphocytes within the PP decreased after the administration of L saerimneri to both wild-type and H2R-deficient animals, while no significant differences were observed in the mesenteric lymph nodes. A nonstatistically significant trend toward reduced IFN-γ+ lymphocytes after the administration of L saerimneri 30a was observed only in PP cells isolated from wild-type animals (n = 6 per group, *P < .05). Journal of Allergy and Clinical Immunology 2014 134, 744-746.e3DOI: (10.1016/j.jaci.2014.04.034) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions