Grant: Operating Grant

Chlamydiae are globally important human bacterial pathogens that cause infectious diseases with serious sequelae. C. pneumoniae (Cpn) is the only chlamydial species causing acquired community pneumonia and possibly atherosclerosis and Alzheimer's disease There is no vaccine for this infection. The lack of a clear understanding of the mechanisms of protective/ pathological reactions has been a major obstacle for the rational development of a vaccine. We recently demonstrated that that Cpn induces significant response of natural killer T cells (NKT) which had a promoting impact on the function of dendritic cells (DC) and T cells which are important for host defense against the infection. We also found that a Cpn lipid antigen can activate NKT. Our objective for the proposed study is to examine mechanism by which NKT promotes the function of DC and T cell responses and protection including bacterial clearance and reduction of pathology. In addition, we will test if the lipid antigen can be used as an adjuvant to enhance the function of current vaccine candidates. We will use mouse model of lung infection with Cpn to examine the interaction of NKT and DCs and the outcome effect on T cell function and protection. Different types of mice including those with deficiency in particular cells and molecules will be tested. We will examine the immune responses, disease process and the outcome of infection in the special and normal control mice. We will also examine the changes related to how the cells look like and how the cell function especially from the aspects related to host dense against chlamydial infections and diseases. The study may lead to identification of new mechanisms and molecules related to chlamydial immunity and pathogenesis. Such knowledge will be very useful for the rational design of an effective and safe chlamydial vaccine.