NK cells contribute to intracellular bacterial infection-mediated inhibition of allergic responses

To experimentally examine the hygiene hypothesis, here we studied the effect of chlamydial infection on the development of allergic responses induced by OVA and the involvement of NK cells in this process using a mouse model of airway inflammation. We found that prior Chlamydia muridarum infection can inhibit airway eosinophilic inflammation and mucus production induced by allergen sensitization and challenge. The inhibition was correlated with an alteration of allergen-driven cytokine-producing patterns of T cells. We demonstrated that NK cells were activated following chlamydial infection, showing both cell expansion and cytokine secretion. The in vivo depletion of NK cells using anti-NK Ab before OVA sensitization and challenge partially abolished the inhibitory effect of chlamydial infection, which was associated with a partial restoration of Th2 cytokine production. In contrast, the adoptive transfer of NK cells that were isolated from infected mice showed a significant inhibitory effect on allergic responses, similar to that observed in natural infection. The data suggest that the innate immune cells such as NK cells may play an important role in infection-mediated inhibition of allergic responses.