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Using our dog model of early life allergen inhalation, we tested the hypothesis that the atopically biased neonatal immune system would exhibit tolerance to ragweed if allowed to mature normally before exposure or artificially through innate immune stimulation with early life exposure. Dogs were subjected to a series of inhalational ragweed exposures from 1 to 20\u00a0weeks old, with or without inhalation of a Toll\u2010like receptor 4 (<jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4) agonist (<jats:styled-content style=\"fixed-case\">CRX<\/jats:styled-content>\u2010527), or from 13 to 31\u00a0weeks old. Serum allergen\u2010specific antibody response was assessed at 4, 8 and 20\u00a0weeks after the last sensitizing exposure. At 24 or 35\u00a0weeks old, airway hyper\u2010responsiveness to methacholine and ragweed challenges and pulmonary inflammation by bronchoalveolar lavage were tested 1 and 4\u00a0days after ragweed challenge at 28 or 39\u00a0weeks old. Allergen\u2010free immune maturation resulted in no airway hyper\u2010responsiveness and very little ragweed\u2010specific IgE relative to the control group, but eosinophilia developed upon ragweed challenge. <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 agonism yielded no airway hyper\u2010responsiveness, but a strong airway neutrophilia developed upon ragweed challenge. Our data indicate that an atopic predisposition creates a critical window in which allergen exposure can lead to an asthmatic phenotype. Allergen\u2010free immune maturation may lead to allergen tolerance. <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 agonism before early life allergen exposure may abrogate the development of allergen\u2010specific bronchonconstriction, but allergen\u2010specific pulmonary inflammation remains a strong concern.<\/jats:p>","DOI":"10.1111\/imm.12043","type":"journal-article","created":{"date-parts":[[2012,11,26]],"date-time":"2012-11-26T19:09:01Z","timestamp":1353956941000},"page":"361-369","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The neonatal susceptibility window for inhalant allergen sensitization in the atopically predisposed canine asthma model"],"prefix":"10.1111","volume":"138","author":[{"given":"Christopher M.","family":"Royer","sequence":"first","affiliation":[{"name":"Respiratory Immunology and Asthma Program Lovelace Respiratory Research Institute Albuquerque NM 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