Chlamydial lung infections are associated with asthma but it is unknown how these Th1-inducing infections influence Th2-mediated asthma. We investigated the effect of current and resolved chlamydial infection on the development of hallmark features of asthma using a murine model of ovalbumin (Ova)-induced AAD.
BALB/c mice were infected with Chlamydia and had either resolved or current respiratory infection at the time of sensitization to Ova. The effect of infection on AAD was compared with un-infected or non-allergic controls.
Current, but not resolved, infection attenuated hallmark features of eosinophilic AAD; pulmonary eosinophil influx, T cell production of IL-5, mucus secreting cell (MSC) hyperplasia and airways hyper-responsiveness (AHR). Importantly, while current infection suppressed Th2-mediated AAD, robust Ova-specific IFN-γ release from T cells and allergen-driven neutrophilic inflammation were induced. This neutrophilic phenotype correlated with increased pulmonary expression of IL-12 and IL-17 and suppression of thymus and activation-related chemokine (TARC). Inhibition of neutrophil and macrophage chemotaxis into the lungs during current infection reversed neutrophilic inflammation and IFN-γ production in AAD and removed the attenuating effect of infection on MSC hyperplasia and AHR. These changes correlated with decreased IL-12 and IL-17 expression, increased TARC and altered antigen presenting cell function.
Ongoing chlamydial respiratory infections modify key allergen-specific immune responses in AAD with the composition of cellular inflammatory responses to infection crucial in determining the outcome of allergic phenotype.
Supported by the NHMRC