Role of Dendritic Cells in Regulating T Cell-mediated Immunity Against Q Fever

Coxiella burnetii is an obligate intracellular Gram-negative bacterium that causes acute and chronic Q fever in humans. There is an urgent need to create a safe and effective vaccine for prevention of human Q fever. However, the mechanisms of vaccine-induced immunity against C. burnetii natural infection remain unclear. The long-term goal of this project is to develop a safe and effective vaccine against Q fever. The objective of this application, which is a critical step towards this goal, is to understand the role of dendritic cells (DCs) in regulating vaccine-induced immunity against Q fever and identify which type of T cell response is more critical for vaccine-induced protective immunity. To achieve this objective, two specific aims were proposed to test the central hypothesis that C. burnetii phase I vaccine (PIV) and phase II vaccine (PIIV) differentially activate DCs, thereby promoting distinct T cell responses are responsible for the difference in their ability to confer protection. Aim 1 will determine the role of DCs in regulating vaccine-induced immunity against Q fever by examining i) if PIV and PIIV differentially activate DCs, thereby promoting distinct T cell differentiation patterns in a mouse model; and ii) if DCs play a role in vaccine-induced protection against C. burnetii aerosol infection in vivo. Aim 2 will determine the role of CD4+ T cell subsets in PIV-induced protective immunity against C. burnetii aerosol infection by using a mouse model to investigate i) if PIV- and PIIV-induced T cell responses are responsible for the difference in their ability to confer protection; and ii) which CD4+ subset T cell response is more critical for PIV-induced protection. As an outcome of this research, it will gain novel information for understanding the role of DCs in regulating T cell-mediated immunity and determining the role of T cell responses in vaccine-induced protective immunity against C. burnetii infection. This is expected to have significant positive effects on publich health, because it will provide critical information for developing a safe and effective vaccine against Q fever.