期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 122, 期 3, 页码 595-602出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2008.06.038
关键词
asthma; allergic sensitization; adjuvant; dendritic cell; Chlamydia pneumoniae; regulatory T cells; bacterial pneumonia; allergen
资金
- National Institutes of Health [AI067995, AI058128, HL66436]
- UCLA Asthma and Allergic Disease Clinical Research Center [AI50495]
- Deutsche Forschungsgemeinschaft (DFG) [Schr 726/2]
Background: The original hygiene hypothesis predicts that infections should protect against asthma but does not account for increasing evidence that certain infections might also promote asthma development. A mechanistic reconciliation of these findings has not yet emerged. In particular, the role of innate immunity in this context is unclear. Objective: We sought to test whether bacterial respiratory tract infection causes airway sensitization toward an antigen encountered in parallel and to elucidate the contribution of innate immune responses. Methods: Mice were infected with different doses of Chlamydia pneumoniae, followed by exposure to human serum albumin (HSA) and challenge with HSA 2 weeks later. Airway inflammation, immunoglobulins, and lymph node cytokines were assessed. Furthermore, adoptive transfer of dendritic cells (DCs) and depletion of regulatory T (Treg) cells was performed. Results: C pneumoniae-induced lung inflammation triggered sensitization toward HSA, resulting in eosinophilic airway inflammation after HSA challenge. Airway sensitization depended on the severity and timing of infection: low-dose infection and antigen exposure within 5 days of infection induced allergic sensitization, whereas high-dose infection or antigen exposure 10 days after infection did not. Temporal and dose-related effects reflected DC activation and could be reproduced by means of adoptive transfer of HSA-pulsed lung DCs from infected mice. MyD88 deficiency in DCs abolished antigen sensitization, and depletion of Treg cells prolonged the time window in which sensitization could occur. Conclusions: We conclude that moderate, but not severe, pulmonary bacterial infection can induce allergic sensitization to inert inhaled antigens through a mechanism that requires MyD88-dependent DC activation and is controlled by Treg cells.
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