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

Abstract

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 TH2 cytokines including IL-4, IL-13 and IL-5. Treatment with KB attenuated HDM-mediated airway eosinophilia, total bronchoalveolar lavage (BAL) cell numbers, BAL TH2 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.

Attenuating immune pathology using a microbial-based intervention in a mouse model of cigarette smoke-induced lung inflammation

“…This has primarily been demonstrated in animal models of allergic airway disease where different treatment strategies using bacteria or bacterial derived products have been used to modulate immune responses [20–22, 24]. Towards that end, intervention strategies encompassing everything from live bacteria to specific pattern recognition receptor agonists have been used in models of allergic airway disease [21, 22, 25–27]. The apparent mechanism of action works through a reduction in inflammation and an altering of the immune response.…”

The right microbial stimulus can direct innate immune effector cells to specific organ sites to clear pathology

“…The discovery of tissue-specific microbial memory that can be therapeutically exploited to direct trained innate immune effector cells to sites of pathology has the potential to change the way diseases rooted in immune dysfunction are treated. In addition to treating various cancers and infections, proof-of-principle experiments conducted to date show promise for this approach for the treatment of asthma [32], COPD [33], and inflammatory bowel disease [34]. The clinical application of this immunotherapeutic strategy has been promising thus far, based on Phase 1 and 2 studies in non-small cell lung cancer [8], ulcerative colitis [35], and Crohn’s disease [36].…”

“…QBKPN is a proprietary investigational immunotherapeutic formulated from an inactivated clinical lung isolate of Klebsiella variicola acquired from a patient with pneumonia [8,32,33]. QBECO is a similarly manufactured proprietary investigational immunotherapeutic made from an inactivated clinical isolate of Escherichia coli from a patient with bloody diarrhea.…”

Tropomiosina de barata Periplaneta americana: papel na imunoterapia sublingual em modelo experimental de hiper-responsividade brônquica e na investigação da resposta IgE em pacientes com dermatite atópica

“…Esse tipo de resposta induzida pelas citocinas IL-25 e IL-33 é caracterizada pela produção das interleucinas IL-4, IL-5 e IL-13, pela produção de anticorpos IgE alérgeno-específicos e pela ativação de basófilos, mastócitos e eosinófilos. Outras interleucinas também são importantes na doença como a IL-9, IL-22 e IL-17 (MARTINS, 2015;FARAHANI et al, 2014;BAZETT et al, 2016;KAPPEN et al, 2016;OZDEMIR et al, 2016).…”

“…Esses alérgenos podem ser administrados na forma de proteína recombinante ou como extrato bruto. O uso da proteína recombinante é preferido por permitir o uso somente da molécula alergênica(MARTINS, 2015;HIROTA et al, 2011;BAZETT et al, 2016). Interessados principalmente no papel preventivo da ITSL, Hagner et al (2016) mostraram que esta terapia é eficaz tanto no combate à inflamação das vias aéreas quanto na prevenção usando modelo experimental de sensibilização e desafio intranasais com extrato de Dermatophagoides farinae.…”