Neonatal chlamydial infection induces mixed T-cell responses that drive allergic airway disease.
BACKGROUND
Chlamydial lung infection has been associated with asthma in children and adults. However, how chlamydial infection influences the development of immune responses that promote asthma remains unknown.


OBJECTIVE
To determine the effect of chlamydial infection at various ages on the development of allergic airway disease (AAD).


METHODS
Mouse models of chlamydial lung infection and ovalbumin-induced AAD were established in neonatal and adult BALB/c mice. Neonatal or adult mice were given a chlamydial infection and 6 weeks later were sensitized and subsequently challenged with ovalbumin. Features of AAD and inflammation were compared between uninfected or unsensitized controls.


RESULTS
Mild Chlamydia-induced lung disease was observed 10-15 days after infection, as evidenced by increased bacterial numbers and histopathology in the lung and a reduction in weight gain. After 6 weeks, infection and histopathology had resolved and the rate of weight gain had recovered. Neonatal but not adult infection resulted in significant decreases in interleukin-5 production from helper T cells and by the numbers of eosinophils recruited to the lung in response to ovalbumin exposure. Remarkably, the effects of early-life infection were associated with the generation of both type 1 and 2 ovalbumin-specific helper T-cell cytokine and antibody responses. Furthermore, although neonatal infection significantly attenuated eosinophilia, the generation of the mixed T-cell response exacerbated other hallmark features of asthma: mucus hypersecretion and airway hyperresponsiveness. Moreover, infection prolonged the expression of AAD and these effects were restricted to early-life infection.


CONCLUSIONS
Early-life chlamydial infection induces a mixed type 1 and 2 T-cell response to antigen, which differentially affects the development of key features of AAD in the adult.
Horvat
Jay C
JC
Priority Research Centre for Asthma and Respiratory Disease, School of Biomedical Sciences, Faculty of Health, University of Newcastle, Newcastle, Australia.
Beagley
Kenneth W
KW
Wade
Margaret A
MA
Preston
Julie A
JA
Hansbro
Nicole G
NG
Hickey
Danica K
DK
Kaiko
Gerard E
GE
Gibson
Peter G
PG
Foster
Paul S
PS
Hansbro
Philip M
PM
D000818:Animals; D000831:Animals, Newborn; D001249:Asthma / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D002689:Chlamydia / Q000302:isolation & purification; D002690:Chlamydia Infections / Q000276:immunology* / Q000473:pathology; D015169:Colony Count, Microbial; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D007111:Immunity, Cellular / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines