Project description:The overall study examines the mechanism and role of innate re-stimulation of T cells after activation and differentiation during infection. This particular study is focused on the restimulation of Th1 cells activated during Chlamydia infection, using in vivo LPS stimulation to increase the response. The study was conducted to compare the expression profile after LPS stimulation during Chlamydia infection to that seen after LPS stimulation during Salmonella infection (submitted as a separate dataset).
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:ATAC-seq profiling of Nfat5 KO and wild type macrophages derived from bone marrow (primary cells), treated or not with Lipopolysaccharide (LPS).
