Grant: CIHR/Regional Partnership Program/Operating Grants

Chlamydiae are globally important human bacterial pathogens that cause infectious diseases with serious sequelae. The lack of a clear understanding of the mechanisms of protective/ pathological reactions has been a major obstacle for the development of a vaccine. We recently demonstrated that dendritic cells (DCs) and that DC subsets are different in potency to induce protective immunity against chlamydia. Moreover, we found that C. pneumoniae (Cpn), the only chlamydial species causing acquired community pneumonia and possibly causing atherosclerosis and Alzheimer's disease, induced significant natural killr T cells (NKT) response which had dramatic impact on DC function. DCs and NKT are important immune cells in the generation and maintenance of protective immune responses. But the interaction of these cells remains unclear. In the proposed study, our objective is to examine the interaction between NKT and DCs during Cpn infection with a emphasis on the effect of NKT on DC subsets and its impact on T cell responses and disease outcomes. We will use mouse model of lung infection with Chlamydia to examine the interaction of NKT and DCs. Different types of mice including those with deficiency in particular cells and molecules will be used, which allow us to test the role of these cell/molecules in protection. We will examine the immune responses and the outcome of infection in the special and normal mice. We will also examine the changes in cell markers and functions especially those related to host dense against chlamydial infections and diseases. This study will provide insight into the mechanism for functional modulation of DC/DC subsets by NKT in infection. The study may lead to identification of new mechanisms/molecules important for DC function. Such knowledge will be useful for the design of a chlamydial vaccine in particular and be helpful in understanding immune regulation and vaccine development in infectious diseases in general.