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

Kei E. Fujimura; Tine Demoor; Marcus Rauch; Ali A. Faruqi; Sihyug Jang; Christine C. Johnson; Homer A. Boushey; Edward Zoratti; Dennis Ownby; Nicholas W. Lukacs; Susan V. Lynch

doi:10.1073/pnas.1310750111

New Research In

Edited by Ralph R. Isberg, Howard Hughes Medical Institute/Tufts University School of Medicine, Boston, MA, and approved November 19, 2013 (received for review June 6, 2013)

Significance

Early-life exposure to dogs is protective against allergic disease development, and dog ownership is associated with a distinct milieu of house dust microbial exposures. Here, we show that mice exposed to dog-associated house dust are protected against airway allergen challenge. These animals exhibit reduced Th2 cytokine production, fewer activated T cells, and a distinct gut microbiome composition, highly enriched for Lactobacillus johnsonii, which itself can confer airway protection when orally supplemented as a single species. This study supports the possibility that host–environment interactions that govern allergic or infectious airway disease may be mediated, at least in part, by the impact of environmental exposures on the gastrointestinal microbiome composition and, by extension, its impact on the host immune response.

Abstract

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.

Footnotes

↵¹K.E.F. and T.D. contributed equally to this work.
↵²To whom correspondence may be addressed. E-mail: susan.lynch{at}ucsf.edu or nlukacs{at}umich.edu.

Author contributions: T.D., C.C.J., H.A.B., E.Z., D.O., N.W.L., and S.V.L. designed research; K.E.F., T.D., M.R., and S.J. performed research; K.E.F., A.A.F., and C.C.J. contributed new reagents/analytic tools; K.E.F., T.D., M.R., A.A.F., S.J., N.W.L., and S.V.L. analyzed data; and K.E.F., T.D., M.R., N.W.L., and S.V.L. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The microbiome data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE52909).
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1310750111/-/DCSupplemental.

Freely available online through the PNAS open access option.