House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection

Abstract

Exposure to dogs in early infancy has been shown to reduce therisk of childhood allergic disease development, and dog ownershipis associated with a distinct house dust microbial exposure. Here,we demonstrate, using murine models, that exposure of mice todog-associated house dust protects against ovalbumin or cockroach allergen-mediated airway pathology. Protected animalsexhibited significant reduction in the total number of airway Tcells, down-regulation of Th2-related airway responses, as well asmucin secretion. Following dog-associated dust exposure, the cecalmicrobiome of protected animals was extensively restructured withsignificant enrichment of, amongst others, Lactobacillus johnsonii.Supplementation of wild-type animals with L. johnsonii protectedthem against both airway allergen challenge or infection with respiratory syncytial virus. L. johnsonii-mediated protection was associated with significant reductions in the total number and proportion of activated CD11c+/CD11b+ and CD11c+/CD8+ cells, as well assignificantly reduced airway Th2 cytokine expression. Our resultsreveal that exposure to dog-associated household dust results inprotection against airway allergen challenge and a distinct gastrointestinal microbiome composition. Moreover, the study identifiesL. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces ina manner that is protective against a variety of respiratory insults.