Title |
Early-Life Intranasal Colonization with Nontypeable Haemophilus influenzae Exacerbates Juvenile Airway Disease in Mice
|
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Published in |
Infection and Immunity, June 2016
|
DOI | 10.1128/iai.01539-15 |
Pubmed ID | |
Authors |
Jessica R. McCann, Stanley N. Mason, Richard L. Auten, Joseph W. St. Geme, Patrick C. Seed |
Abstract |
Accumulating evidence suggests a connection between asthma development and colonization with nontypeable Haemophilus influenzae (NTHi). Specifically, nasopharyngeal colonization of human infants with NTHi within 4 weeks of birth is associated with an increased risk of asthma development later in childhood. Monocytes derived from these infants have aberrant inflammatory responses to common upper respiratory bacterial antigens when compared to cells derived from infants who were not colonized and do not go on to develop asthma symptoms in childhood. In this study, we hypothesized that early life colonization with NTHi promotes immune system reprogramming and the development of atypical inflammatory responses. To address this hypothesis in a highly controlled model, we tested whether colonization of mice with NTHi on day of life 3 induced or exacerbated juvenile airways disease using an ovalbumin (OVA) allergic model of asthma. We found that animals that were colonized on day of life 3 and subjected to induction of allergy had exacerbated airways disease as juveniles, defined as increased cellular infiltration into the lung, increased inflammatory cytokines IL5 and IL13 in the lung lavage fluid, decreased regulatory T cell-associated FOXP3 gene expression, and increased mucus production. We also found that colonization with NTHi amplified airway resistance in response to increasing doses of a bronchoconstrictor following OVA immunization and challenge. Together, the murine model provides evidence for early life immune programming that precedes the development of juvenile airways disease and corroborates observations in human children. |
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Country | Count | As % |
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Unknown | 23 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 4 | 17% |
Student > Postgraduate | 4 | 17% |
Professor > Associate Professor | 3 | 13% |
Researcher | 2 | 9% |
Student > Bachelor | 2 | 9% |
Other | 2 | 9% |
Unknown | 6 | 26% |
Readers by discipline | Count | As % |
---|---|---|
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Medicine and Dentistry | 5 | 22% |
Biochemistry, Genetics and Molecular Biology | 4 | 17% |
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Nursing and Health Professions | 1 | 4% |
Other | 0 | 0% |
Unknown | 6 | 26% |