A novel microbe-based treatment that attenuates the inflammatory profile in a mouse model of allergic airway disease

• Published in: Scientific reports Vol. 6; no. 1; p. 35338
• Main Authors: Bazett, Mark, Biala, Agnieszka, Huff, Ryan D., Bosiljcic, Momir, Gunn, Hal, Kalyan, Shirin, Hirota, Jeremy A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13-10-2016; Nature Publishing Group
• Subjects: 631/250/127; 631/250/98; 82/79; Allergens; Allergens - immunology; Allergies; Alveoli; Animals; Asthma; Asthma - immunology; Asthma - therapy; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid - immunology; Bronchus; Chemokine CCL11 - metabolism; Cytokines; Dermatophagoides pteronyssinus - immunology; Disease Models, Animal; Eosinophilia; Female; Gene expression; Gene Expression Profiling; House dust; Humanities and Social Sciences; Hyperplasia; Hypersensitivity - immunology; Hypersensitivity - therapy; Immunoglobulin E; Immunoglobulin E - blood; Immunomodulation; Inflammation; Inflammation - immunology; Inflammation - therapy; Interleukin 13; Interleukin 4; Interleukin 5; Interleukin-13 - blood; Interleukin-4 - blood; Interleukin-5 - blood; Klebsiella - metabolism; Medical treatment; Metaplasia; Mice; Mice, Inbred BALB C; Microorganisms; multidisciplinary; Pyroglyphidae - immunology; Respiratory tract diseases; Rodents; Science; Small intestine; Th1 Cells - cytology; Th2 Cells - cytology; Th2 Cells - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep35338

There is an unmet need for effective new and innovative treatments for asthma. It is becoming increasingly evident that bacterial stimulation can have beneficial effects at attenuating allergic airway disease through immune modulation. Our aim was to test the ability of a novel inactivated microbe-derived therapeutic based on
Klebsiella
(KB) in a model of allergic airway disease in mice. BALB/c mice were exposed intranasally to house dust mite (HDM) for two weeks. Mice were treated prophylactically via subcutaneous route with either KB or placebo for one week prior to HDM exposure and throughout the two week exposure period. 24 hours after the last exposure, lungs were analysed for inflammatory cell infiltrate, gene expression, cytokine levels, goblet cell metaplasia, and serum was analysed for allergen-specific serum IgE levels. HDM exposed mice developed goblet cell hyperplasia, elevated allergen-specific serum IgE, airway eosinophilia, and a concomitant increase in T
H
2 cytokines including IL-4, IL-13 and IL-5. Treatment with KB attenuated HDM-mediated airway eosinophilia, total bronchoalveolar lavage (BAL) cell numbers, BAL T
H
2 cytokine production, and goblet cell metaplasia. Our prophylactic intervention study illustrates the potential of subcutaneous treatment with bacterial derived biologics as a promising approach for allergic airway disease treatment.