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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 2; pp. 805 - 810
• Main Authors: Fujimura, Kei E., Demoor, Tine, Rauch, Marcus, Faruqia, Ali A., Jang, Sihyug, Johnson, Christine, Boushey, Homer A., Zoratti, Edward, Ownby, Dennis, Lukacs, Nicholas W., Lyncha, Susan V.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 14-01-2014; National Acad Sciences
• Subjects: Allergic diseases; Allergies; Animal taxonomy; Animals; Biological Sciences; Bronchial Hyperreactivity - immunology; Bronchial Hyperreactivity - prevention & control; Dogs; Dust; Dust - immunology; Environmental Exposure; Flow Cytometry; Fluorescence; Gastrointestinal Tract - microbiology; Human exposure; Immune system; Lactobacillus; Lactobacillus - growth & development; Lactobacillus - immunology; Lactobacillus johnsonii; Lung - pathology; Lungs; Mice; Mice, Inbred BALB C; Microbiota; Microbiota - genetics; Ovalbumin - immunology; Respiratory syncytial virus; Respiratory Syncytial Virus Infections - immunology; Respiratory Syncytial Virus Infections - prevention & control; Reverse Transcriptase Polymerase Chain Reaction; T lymphocytes; Taxa; Th2 Cells - immunology; house environment; Lactobacilliaceae; gastrointestinal bacterial community; airway adaptive immunity
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1310750111

Exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development, and dog ownership is associated with a distinct house dust microbial exposure. Here, we demonstrate, using murine models, that exposure of mice to dog-associated house dust protects against ovalbumin or cockroach allergen-mediated airway pathology. Protected animals exhibited significant reduction in the total number of airway T cells, down-regulation of Th2-related airway responses, as well as mucin secretion. Following dog-associated dust exposure, the cecal microbiome of protected animals was extensively restructured with significant enrichment of, amongst others, Lactobacillus johnsonii . Supplementation of wild-type animals with L. johnsonii protected them 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 as significantly reduced airway Th2 cytokine expression. Our results reveal that exposure to dog-associated household dust results in protection against airway allergen challenge and a distinct gastrointestinal microbiome composition. Moreover, the study identifies L. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces in a manner that is protective against a variety of respiratory insults.