Project description:Effective host defense against infection relies on the tight coordination of immune activation, metabolic adaptation, and redox control, yet how these processes are integrated remains incompletely understood. Here, we identify dipeptidyl peptidase 3 (Dpp3) as a negative regulator of antimicrobial immunity. Dpp3-/- mice exhibit enhanced resistance to Klebsiella pneumoniae infection, with reduced bacterial burden, preserved tissue integrity, and attenuated systemic inflammation. This response is associated with increased phagocytic activity, expansion of germinal centres and plasma cells, and elevated interferon-γ production by T cells. Mechanistically, Dpp3 deficiency leads to reduced Nrf2 protein levels upon stimulation, resulting in heightened ROS accumulation and amplified NF-κB signaling. Integrated metabolomic and transcriptomic analyses of Dpp3-/- immune cells reveal mitochondrial dysfunction and a shift toward biosynthetic and antioxidant-supportive metabolic programs. Collectively, our findings identify Dpp3 as a molecular brake on host defense and uncover a regulatory axis linking redox balance, immunometabolism, and inflammation during infection.
Project description:We inflicted TBI to chemokine-deficient mouse lines in order to establish involvement of various signalling pathways that may be addressed therapeutically. Interacting chemokine pathways in brain regulate distinct inflammatory cells. Activated microglia are separate from invading phagocytes and dendritic cells. Findings show potential targets to interfere with specific inflammatory responses after brain injury.
