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.
Highlights
Environment[14,15]
We investigated the efficacy of a KB therapeutic at attenuating allergic sensitization and TH2-skewed lung inflammation in a house dust mite (HDM) murine model
Increasing evidence suggests that microbial exposures impact the development of the immune system and modulate the risk for developing allergic asthma[16,31], which has led to the hypothesis that treatment of such disorders could involve agents that stimulate, rather than suppress, the immune system[21]
Summary
Environment[14,15] This perspective is consistent with the finding that children at risk for developing asthma have altered intestinal microbiomes[16], which have been attributed to the use of formula, probiotics, and/or antibiotics[17]. We investigated whether using a novel therapeutic derived from a microbial species, Klebsiella (KB), that commonly causes lung infections would improve the immune dysfunction in an established asthma model. We demonstrate that a prophylactic subcutaneous intervention with a novel therapeutic derived from Klebsiella attenuates the development of TH2 lung and systemic inflammation, and associated lung pathology, while not inhibiting allergic sensitization. Our data is consistent with the hypothesis that bacterial derived therapeutics are able to diminish immune dysfunction in allergic airway disease, providing a potential new treatment option to be further investigated in additional studies, including in models of established airway disease
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