| As the prevalence of infectious diseases is reduced in many countries, the incidence of allergic disorders is increasing rapidly in the last several decades, especially in developed countries. The molecular and cellular mechanisms underlying this inverse relationship between microbial exposure and allergic reactions have not been defined. In the present study, we tested experimentally the effect of exposure to Chlamydia muridarum (MoPn) on the development of allergic responses induced by ovalbumin (OVA) exposure and the potential underlying mechanisms.;Our data further suggested that dendritic cells (DC) from adult mice with neonatal exposure to UV-killed C. muridarum exhibited upregulated expression of surface maturation markers (CD80, CD86) and cytokine secretion (IL-12, IL-10), as well as enhanced ability of inhibiting the development of allergic responses upon allergen exposure, compared to those from adult mice without neonatal microbial exposure. Our data indicated that modulating DC function is a key mechanism by which early exposed bacterial components prevent adulthood allergic responses.;We then found that natural killer (NK) cells, another type of key innate cells, play an important role in modulating the function of DC in C. muridarum lung infection by influencing the phenotypic maturation and functional capacity of DC following C. muridarum infection.;Finally, we examined the effect and possible underlying mechanisms of NK cells on modulating the ability of DC from C. muridarum-infected mice to inhibit allergic responses. Our data demonstrated that DC from C. muridarum-infected, and NK-depleted mice exhibited hampered phenotypic maturation, reduced ability to suppress the Th2-dominant responses in both in vitro and in vivo experiments. Collectively, our data show that NK cell plays a key role in C. muridarum infection-mediated inhibition of allergic responses via modulating the functional properties of DC.;Firstly, we tested the effect of neonatal exposure to UV-killed C. muridarum (UV-MoPn) on the development of allergic reactions induced by OVA exposure in adult life. Our data showed that OVA-induced airway eosinophilia and mucus overproduction, as well as allergen-driven T-helper type 2 (Th2) cytokine (IL-4, IL-5 and IL-13) production in adult mice were significantly suppressed by neonatal exposure to UV-MoPn.;Taken together, the data suggest that innate cells activated by C. muridarum lung infection, specifically DC and NK cells, play import roles in host defense against MoPn infection, and have significant modulating effect on allergen driven T cell responses and allergic inflammation. |
