Innate immune responses during respiratory tract infection with a bacterial pathogen induce allergic airway sensitization

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:122

Article

Yilmaz, Atilla³  Slepenkin, Anatoly⁴  Alsabeh, Randa^1,2  Peterson, Ellena⁴  Nel, Andre E.⁵ 

[1] Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90048 USA

[2] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Lab Med, Los Angeles, CA 90048 USA

[3] Univ Erlangen Nurnberg, Med Clin 2, Erlangen, Germany

[4] Univ Calif Irvine, Dept Pathol, Irvine, CA 92717 USA

[5] Univ Calif Los Angeles, Dept Med, Div Clin Immunol & Allergy, Los Angeles, CA 90024 USA

关键词: asthma;    allergic sensitization;    adjuvant;    dendritic cell;    Chlamydia pneumoniae;    regulatory T cells;    bacterial pneumonia;    allergen;   

DOI  :  10.1016/j.jaci.2008.06.038

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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