TY - JOUR
T1 - House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection
AU - Fujimura, Kei E.
AU - Demoor, Tine
AU - Rauch, Marcus
AU - Faruqi, Ali A.
AU - Jang, Sihyug
AU - Johnson, Christine C.
AU - Boushey, Homer A.
AU - Zoratti, Edward
AU - Ownby, Dennis
AU - Lukacs, Nicholas W.
AU - Lynch, Susan V.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Airway adaptive immunity
KW - Gastrointestinal bacterial community
KW - House environment
KW - Lactobacilliaceae
UR - http://www.scopus.com/inward/record.url?scp=84892562813&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84892562813&partnerID=8YFLogxK
U2 - 10.1073/pnas.1310750111
DO - 10.1073/pnas.1310750111
M3 - Article
C2 - 24344318
AN - SCOPUS:84892562813
SN - 0027-8424
VL - 111
SP - 805
EP - 810
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 2
ER -