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

Abstract

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.

• Authors: Nicolas W J Schröder, Timothy R Crother, Yoshikazu Naiki, Shuang Chen, Michelle H Wong, Atilla Yilmaz, Anatoly Slepenkin, Danica Schulte, Randa Alsabeh, Terence M Doherty, Ellena Peterson, Andre E Nel, Moshe Arditi
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 122 Issue 3 Pg. 595-602.e5 (Sep 2008) ISSN: 1097-6825 [Electronic] United States
• PMID: 18774395 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Myd88 protein, mouse
• Myeloid Differentiation Factor 88
• Serum Albumin
• Immunoglobulin E

Topics

• Animals
• Chlamydophila Infections (immunology)
• Chlamydophila pneumoniae (immunology)
• Dendritic Cells (immunology, metabolism)
• Eosinophils (immunology, metabolism)
• Humans
• Immunity, Innate
• Immunoglobulin E (blood)
• Inflammation (complications, immunology)
• Lung (immunology, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Myeloid Differentiation Factor 88 (deficiency, metabolism)
• Respiratory Hypersensitivity (complications, immunology)
• Respiratory Tract Infections (complications, immunology, microbiology)
• Serum Albumin (immunology)
• T-Lymphocytes, Regulatory (immunology, metabolism)