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

J Allergy Clin Immunol. 2008 Sep;122(3):595-602.e5. doi: 10.1016/j.jaci.2008.06.038.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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


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