Innate immune responses during respiratory tract infection with a bacterial pathogen induce allergic airway sensitization.
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.
Schröder
Nicolas W J
NW
Pediatric Infectious Diseases, Cedars-Sinai Medical Center, University of California, Los Angeles, CA, USA.
Crother
Timothy R
TR
Naiki
Yoshikazu
Y
Chen
Shuang
S
Wong
Michelle H
MH
Yilmaz
Atilla
A
Slepenkin
Anatoly
A
Schulte
Danica
D
Alsabeh
Randa
R
Doherty
Terence M
TM
Peterson
Ellena
E
Nel
Andre E
AE
Arditi
Moshe
M
D000818:Animals; D023521:Chlamydophila Infections / Q000276:immunology*; D016993:Chlamydophila pneumoniae / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000150:complications / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000150:complications / Q000276:immunology*; D012141:Respiratory Tract Infections / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D012709:Serum Albumin / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012709:Serum Albumin; D007073:Immunoglobulin E
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